The domain within your query sequence starts at position 42 and ends at position 123; the E-value for the MHC_II_alpha domain shown below is 2.83e-19.

HTFRHTLFCQDGIPNIGLSETYDEDELFSFDFSQNTRVPRLPDFAEWAQGQGDASAIAFD
KSFCEMLMREVSPKLEGQIPVS

MHC_II_alpha

Class II histocompatibility antigen, alpha domain

• SMART accession number: SM00920
• Description: Class II MHC glycoproteins are expressed on the surface of antigen-presenting cells (APC), including macrophages, dendritic cells and B cells. MHC II proteins present peptide antigens that originate extracellularly from foreign bodies such as bacteria. Proteins from the pathogen are degraded into peptide fragments within the APC, which sequesters these fragments into the endosome so they can bind to MHC class II proteins, before being transported to the cell surface. MHC class II receptors display antigens for recognition by helper T cells (stimulate development of B cell clones) and inflammatory T cells (cause the release of lymphokines that attract other cells to site of infection) (PUBMED:15120183).
• Interpro abstract (IPR001003):

  Class II MHC glycoproteins are expressed on the surface of antigen-presenting cells (APC), including macrophages, dendritic cells and B cells. MHC II proteins present peptide antigens that originate extracellularly from foreign bodies such as bacteria. Proteins from the pathogen are degraded into peptide fragments within the APC, which sequesters these fragments into the endosome so they can bind to MHC class II proteins, before being transported to the cell surface. MHC class II receptors display antigens for recognition by helper T cells (stimulate development of B cell clones) and inflammatory T cells (cause the release of lymphokines that attract other cells to site of infection) [ (PUBMED:15120183) ].

  MHC class II molecules are comprised of two membrane-spanning chains, alpha and beta, of similar size. Both chains consist of two globular domains (N- and C-terminal), and a transmembrane segment to anchor them to the membrane [ (PUBMED:7612235) ]. A groove in the structure acts as the peptide-binding site.

  Major Histocompatibility Complex (MHC) glycoproteins are heterodimeric cell surface receptors that function to present antigen peptide fragments to T cells responsible for cell-mediated immune responses. MHC molecules can be subdivided into two groups on the basis of structure and function: class I molecules present intracellular antigen peptide fragments (~10 amino acids) on the surface of the host cells to cytotoxic T cells; class II molecules present exogenously derived antigenic peptides (~15 amino acids) to helper T cells. MHC class I and II molecules are assembled and loaded with their peptide ligands via different mechanisms. However, both present peptide fragments rather than entire proteins to T cells, and are required to mount an immune response.

  This entry represents the N-terminal domain (also called alpha-1 domain) of the alpha chain.

• GO process: antigen processing and presentation (GO:0019882), immune response (GO:0006955)
• GO component: MHC class II protein complex (GO:0042613), membrane (GO:0016020)

There are 2489 MHC_II_alpha domains in 2483 proteins in SMART's nrdb database.

Cellular role (predicted cellular role)

Cellular role: interaction

Literature (relevant references for this domain)

Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

• Holling TM, Schooten E, van Den Elsen PJ
• Function and regulation of MHC class II molecules in T-lymphocytes: ofmice and men.
• Hum Immunol. 2004; 65: 282-90

The main function of major histocompatibility complex (MHC) class IImolecules is to present processed antigens, which are derived primarilyfrom exogenous sources, to CD4(+) T-lymphocytes. MHC class II moleculesthereby are critical for the initiation of the antigen-specific immuneresponse. Besides antigen presentation, growing evidence is showing thatligation of MHC class II molecules also activates intracellular signalingpathways, frequently leading to apoptosis. Constitutive expression of MHCclass II molecules is confined to professional antigen-presenting cells(APC) of the immune system, and in nonprofessional APCs MHC class IImolecules can be induced by a variety of immune regulators. Interestingly,activated T cells from many species, with the exception of mice,synthesize and express MHC class II molecules at their cell surface. Inthis review, we discuss our current knowledge on the transcriptionalregulation of MHC class II expression in activated human and mouse Tcells, and the contribution of DNA methylation of the T-cell employedclass II transactivator promoter III to the MHC class II deficiency ofmouse T cells. We also discuss the proposed functions of the activated Tcell synthesized and expressed MHC class II molecules, including antigenpresentation, T-T cell interactions, and MHC class II-mediatedintracellular signaling.

• Stern LJ et al.
• Crystal structure of the human class II MHC protein HLA-DR1 complexed withan influenza virus peptide.
• Nature. 1994; 368: 215-21

An influenza virus peptide binds to HLA-DR1 in an extended conformationwith a pronounced twist. Thirty-five per cent of the peptide surface isaccessible to solvent and potentially available for interaction with theantigen receptor on T cells. Pockets in the peptide-binding siteaccommodate five of the thirteen side chains of the bound peptide, andexplain the peptide specificity of HLA-DR1. Twelve hydrogen bonds betweenconserved HLA-DR1 residues and the main chain of the peptide provide auniversal mode of peptide binding, distinct from the strategy used byclass I histocompatibility proteins.

Structure (3D structures containing this domain)

3D Structures of MHC_II_alpha domains in PDB

PDB code	Title
1a6a	THE STRUCTURE OF AN INTERMEDIATE IN CLASS II MHC MATURATION: CLIP BOUND TO HLA-DR3
1aqd	HLA-DR1 (DRA, DRB1 0101) HUMAN CLASS II HISTOCOMPATIBILITY PROTEIN (EXTRACELLULAR DOMAIN) COMPLEXED WITH ENDOGENOUS PEPTIDE
1bx2	CRYSTAL STRUCTURE OF HLA-DR2 (DRA*0101,DRB1*1501) COMPLEXED WITH A PEPTIDE FROM HUMAN MYELIN BASIC PROTEIN
1d5m	X-RAY CRYSTAL STRUCTURE OF HLA-DR4 COMPLEXED WITH PEPTIDE AND SEB
1d5x	X-RAY CRYSTAL STRUCTURE OF HLA-DR4 COMPLEXED WITH DIPEPTIDE MIMETIC AND SEB
1d5z	X-RAY CRYSTAL STRUCTURE OF HLA-DR4 COMPLEXED WITH PEPTIDOMIMETIC AND SEB
1d6e	CRYSTAL STRUCTURE OF HLA-DR4 COMPLEX WITH PEPTIDOMIMETIC AND SEB
1d9k	CRYSTAL STRUCTURE OF COMPLEX BETWEEN D10 TCR AND PMHC I-AK/CA
1dlh	CRYSTAL STRUCTURE OF THE HUMAN CLASS II MHC PROTEIN HLA-DR1 COMPLEXED WITH AN INFLUENZA VIRUS PEPTIDE
1es0	CRYSTAL STRUCTURE OF THE MURINE CLASS II ALLELE I-A(G7) COMPLEXED WITH THE GLUTAMIC ACID DECARBOXYLASE (GAD65) PEPTIDE 207-220
1f3j	HISTOCOMPATIBILITY ANTIGEN I-AG7
1fne	HISTOCOMPATIBILITY ANTIGEN
1fng	HISTOCOMPATIBILITY ANTIGEN
1fv1	STRUCTURAL BASIS FOR THE BINDING OF AN IMMUNODOMINANT PEPTIDE FROM MYELIN BASIC PROTEIN IN DIFFERENT REGISTERS BY TWO HLA-DR2 ALLELES
1fyt	CRYSTAL STRUCTURE OF A COMPLEX OF A HUMAN ALPHA/BETA-T CELL RECEPTOR, INFLUENZA HA ANTIGEN PEPTIDE, AND MHC CLASS II MOLECULE, HLA-DR1
1h15	X-ray crystal structure of HLA-DRA1*0101/DRB5*0101 complexed with a peptide from Epstein Barr Virus DNA polymerase.
1hdm	HISTOCOMPATIBILITY ANTIGEN HLA-DM
1hqr	CRYSTAL STRUCTURE OF A SUPERANTIGEN BOUND TO THE HIGH-AFFINITY, ZINC-DEPENDENT SITE ON MHC CLASS II
1hxy	CRYSTAL STRUCTURE OF STAPHYLOCOCCAL ENTEROTOXIN H IN COMPLEX WITH HUMAN MHC CLASS II
1i3r	CRYSTAL STRUCTURE OF A MUTANT IEK CLASS II MHC MOLECULE
1iak	HISTOCOMPATIBILITY ANTIGEN I-AK
1iao	CLASS II MHC I-AD IN COMPLEX WITH OVALBUMIN PEPTIDE 323-339
1iea	HISTOCOMPATIBILITY ANTIGEN
1ieb	HISTOCOMPATIBILITY ANTIGEN
1j8h	Crystal Structure of a Complex of a Human alpha/beta-T cell Receptor, Influenza HA Antigen Peptide, and MHC Class II Molecule, HLA-DR4
1jk8	Crystal structure of a human insulin peptide-HLA-DQ8 complex
1jl4	CRYSTAL STRUCTURE OF THE HUMAN CD4 N-TERMINAL TWO DOMAIN FRAGMENT COMPLEXED TO A CLASS II MHC MOLECULE
1jwm	Crystal Structure of the Complex of the MHC Class II Molecule HLA-DR1(HA peptide 306-318) with the Superantigen SEC3
1jws	Crystal Structure of the Complex of the MHC Class II Molecule HLA-DR1 (HA peptide 306-318) with the Superantigen SEC3 Variant 3B1
1jwu	Crystal Structure of the Complex of the MHC Class II Molecule HLA-DR1 (HA peptide 306-318) with the superantigen SEC3 Variant 3B2
1k2d	Crystal structure of the autoimmune MHC class II I-Au complexed with myelin basic protein 1-11 at 2.2A
1k8i	CRYSTAL STRUCTURE OF MOUSE H2-DM
1kg0	Structure of the Epstein-Barr Virus gp42 Protein Bound to the MHC class II Receptor HLA-DR1
1klg	Crystal structure of HLA-DR1/TPI(23-37, Thr28-->Ile mutant) complexed with staphylococcal enterotoxin C3 variant 3B2 (SEC3-3B2)
1klu	Crystal structure of HLA-DR1/TPI(23-37) complexed with staphylococcal enterotoxin C3 variant 3B2 (SEC3-3B2)
1kt2	CRYSTAL STRUCTURE OF CLASS II MHC MOLECULE IEK BOUND TO MOTH CYTOCHROME C PEPTIDE
1ktd	CRYSTAL STRUCTURE OF CLASS II MHC MOLECULE IEK BOUND TO PIGEON CYTOCHROME C PEPTIDE
1lnu	CRYSTAL STRUCTURE OF CLASS II MHC MOLECULE IAb BOUND TO EALPHA3K PEPTIDE
1lo5	Crystal structure of the D227A variant of Staphylococcal enterotoxin A in complex with human MHC class II
1muj	Crystal structure of murine class II MHC I-Ab in complex with a human CLIP peptide
1pyw	Human class II MHC protein HLA-DR1 bound to a designed peptide related to influenza virus hemagglutinin, FVKQNA(MAA)AL, in complex with staphylococcal enterotoxin C3 variant 3B2 (SEC3-3B2)
1r5i	Crystal structure of the MAM-MHC complex
1r5v	Evidence that structural rearrangements and/or flexibility during TCR binding can contribute to T-cell activation
1r5w	Evidence that structural rearrangements and/or flexibility during TCR binding can contribute to T-cell activation
1s9v	Crystal structure of HLA-DQ2 complexed with deamidated gliadin peptide
1seb	COMPLEX OF THE HUMAN MHC CLASS II GLYCOPROTEIN HLA-DR1 AND THE BACTERIAL SUPERANTIGEN SEB
1sje	HLA-DR1 complexed with a 16 residue HIV capsid peptide bound in a hairpin conformation
1sjh	HLA-DR1 complexed with a 13 residue HIV capsid peptide
1t5w	HLA-DR1 in complex with a synthetic peptide (AAYSDQATPLLLSPR)
1t5x	HLA-DR1 in complex with a synthetic peptide (AAYSDQATPLLLSPR) and the superantigen SEC3-3B2
1u3h	Crystal structure of mouse TCR 172.10 complexed with MHC class II I-Au molecule at 2.4 A
1uvq	Crystal structure of HLA-DQ0602 in complex with a hypocretin peptide
1ymm	TCR/HLA-DR2b/MBP-peptide complex
1zgl	Crystal structure of 3A6 TCR bound to MBP/HLA-DR2a
2bc4	Crystal structure of HLA-DM
2fse	Crystallographic structure of a rheumatoid arthritis MHC susceptibility allele, HLA-DR1 (DRB1*0101), complexed with the immunodominant determinant of human type II collagen
2g9h	Crystal Structure of Staphylococcal Enterotoxin I (SEI) in Complex with a Human MHC class II Molecule
2iad	CLASS II MHC I-AD IN COMPLEX WITH AN INFLUENZA HEMAGGLUTININ PEPTIDE 126-138
2iam	Structural basis for recognition of mutant self by a tumor-specific, MHC class II-restricted TCR
2ian	Structural basis for recognition of mutant self by a tumor-specific, MHC class II-restricted TCR
2icw	Crystal structure of a complete ternary complex between TCR, superantigen, and peptide-MHC class II molecule
2ipk	Crystal Structure of the MHC Class II Molecule HLA-DR1 in Complex with the Fluorogenic Peptide, AcPKXVKQNTLKLAT (X=3-[5-(dimethylamino)-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl]-L-alanine) and the Superantigen, SEC3 Variant 3B2
2nna	Structure of the MHC class II molecule HLA-DQ8 bound with a deamidated gluten peptide
2oje	Mycoplasma arthritidis-derived mitogen complexed with class II MHC molecule HLA-DR1/HA complex in the presence of EDTA
2p24	I-Au/MBP125-135
2pxy	Crystal structures of immune receptor complexes
2q6w	The structure of HLA-DRA, DRB3*0101 (DR52a) with bound platelet integrin peptide associated with fetal and neonatal alloimmune thrombocytopenia
2seb	X-RAY CRYSTAL STRUCTURE OF HLA-DR4 COMPLEXED WITH A PEPTIDE FROM HUMAN COLLAGEN II
2wbj	TCR complex
2xn9	Crystal structure of the ternary complex between human T cell receptor, staphylococcal enterotoxin H and human major histocompatibility complex class II
2z31	Crystal structure of immune receptor complex
3c5j	Crystal structure of HLA DR52c
3c5z	Crystal structure of mouse MHC class II I-Ab/3K peptide complexed with mouse TCR B3K506
3c60	Crystal structure of mouse MHC class II I-Ab/3K peptide complexed with mouse TCR YAe62
3c6l	Crystal structure of mouse MHC class II I-Ab/3K peptide complexed with mouse TCR 2W20
3cup	Crystal structure of the MHC class II molecule I-Ag7 in complex with the peptide GAD221-235
3l6f	Structure of MHC class II molecule HLA-DR1 complexed with phosphopeptide MART-1
3lqz	Crystal Structure of HLA-DP2
3mbe	TCR 21.30 in complex with MHC class II I-Ag7HEL(11-27)
3o6f	Crystal structure of a human autoimmune TCR MS2-3C8 bound to MHC class II self-ligand MBP/HLA-DR4
3pdo	Crystal Structure of HLA-DR1 with CLIP102-120
3pgc	Crystal Structure of HLA-DR1 with CLIP106-120, flipped peptide orientation
3pgd	Crystal Structure of HLA-DR1 with CLIP106-120, canonical peptide orientation
3pl6	Structure of Autoimmune TCR Hy.1B11 in complex with HLA-DQ1 and MBP 85-99
3qib	Crystal structure of the 2B4 TCR in complex with MCC/I-Ek
3qiu	Crystal structure of the 226 TCR in complex with MCC/I-Ek
3qiw	Crystal structure of the 226 TCR in complex with MCC-p5E/I-Ek
3qxa	HLA-DR1 bound with CLIP peptide
3qxd	F54C HLA-DR1 bound with CLIP peptide
3rdt	Crystal Structure of 809.B5 TCR complexed with MHC Class II I-Ab/3k peptide
3s4s	Crystal structure of CD4 mutant bound to HLA-DR1
3s5l	Crystal structure of CD4 mutant bound to HLA-DR1
3t0e	Crystal structure of a complete ternary complex of T cell receptor, peptide-MHC and CD4
3wex	3WEX
4aen	HLA-DR1 with covalently linked CLIP106-120 in reversed orientation
4ah2	HLA-DR1 with covalently linked CLIP106-120 in canonical orientation
4c56	4C56
4d8p	Structural and functional studies of the trans-encoded HLA-DQ2.3 (DQA1*03:01/DQB1*02:01) molecule
4e41	Structural basis for the recognition of mutant self by a tumor-specific, MHC class II-restricted T cell receptor G4
4fqx	Crystal structure of HLA-DM bound to HLA-DR1
4gbx	Crystal structure of an immune complex at pH 6.5
4gg6	Protein complex
4grl	Crystal structure of a autoimmune TCR-MHC complex
4h1l	TCR interaction with peptide mimics of nickel offers structural insights in nickel contact allergy
4h25	TCR interaction with peptide mimics of nickel offers structure insights to nickel contact allergy
4h26	TCR interaction with peptide mimics of nickel offers structure insight to nickel contact allergy
4i0p	HLA-DO in complex with HLA-DM
4i5b	Structure of human MHC class II protein HLA-DR1 carrying an influenza hemagglutinin peptide partially filling the binding groove
4is6	Crystal structure of HLA-DR4 bound to GP100 peptide
4may	Crystal structure of an immune complex
4mcy	Immune Receptor
4mcz	Immune Receptor
4md0	Immune Receptor
4md4	Immune Receptor
4md5	Immune Receptor
4mdi	Immune Receptor
4mdj	Immune Receptor
4ov5	4OV5
4ozf	JR5.1 protein complex
4ozg	D2 protein complex
4ozh	S16 protein complex
4ozi	S2 protein complex
4p23	4P23
4p2o	Crystal structure of the 2B4 TCR in complex with 2A/I-Ek
4p2q	Crystal structure of the 5cc7 TCR in complex with 5c2/I-Ek
4p2r	Crystal structure of the 5cc7 TCR in complex with 5c1/I-Ek
4p46	4P46
4p4k	4P4K
4p4r	4P4R
4p57	4P57
4p5k	4P5K
4p5m	4P5M
4p5t	4P5T
4x5w	4X5W
4x5x	4X5X
4y19	4Y19
4y1a	4Y1A
4z7u	4Z7U
4z7v	4Z7V
4z7w	4Z7W
5dmk	5DMK
5ks9	5KS9
5ksa	5KSA
5ksb	5KSB

Links (links to other resources describing this domain)

• PFAM: MHC_II_alpha
• INTERPRO: IPR001003