The Major Histocompatibility Complex (Human Leukocyte Antigen HLA)

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MHC Class I and Class II Proteins

MHC Class I and Class II Proteins

Class I
Alpha Chain
3 External domains 1 Transmembrane 1 Cytoplasmic tail Encoded in MHC 1 External domain No transmembrane No Cytoplasmic tail Not encoded in MHC

Class II
Alpha Chain
2 External domains 1 Transmembrane 1 Cytoplasmic Tail Encoded in MHC 2 External domains 1 Transmembrane 1 Cytoplasmic Tail Encoded in MHC

Beta-2 Microglobulin

Beta Chain

MHC Class I and Class II Proteins

Class I
Tissue Distribution
All nucleated cells RBCs in some species

Class II
Tissue Distribution
Antigen presenting cells Macrophages Dendritic cells B cells Thymic Epithelium

Function
Presentation of antigens to CD8+ T cells

Function
Presentation of antigens to CD4+ T cells

MHC Polymorphism
Both Class I and Class II genes are highly polymorphic Most polymorphic residues of Class I are in the alpha 1 and alpha 2 domains Most polymorphic residues of Class II are in the alpha 1 and beta 1 domains

MHC

Genetics
The MHC is the most polymorphic genetic system known

Location of Polymorphic Residues

Location of Polymorphic Residues

MHC Polymorphism
Polymorphism at site of peptide contact
Alters the repertoire of peptides that can bind Increases repertoire of antigens that can be recognized within a population

Polymorphism at the site of TCR contact

Increases chance of TCR:MHC/peptide recognition Results in experimental observations of MHC restriction

MHC Polymorphism

MHC Class I, II & III Genes

MHC Class I, II, III & IV Genes

MHC Recombinant Inbred Mice

MHC Class I DNA, RNA and Protein

MHC Class II DNA, RNA and Protein

Class I:Peptide Binding

Class I:Peptide Binding

MHC class I molecules present peptides from endogenously synthesized proteins

MHC class II molecules present peptides from exogenously derived proteins

Class III MHC Proteins

Complement components Steroid hydroxylase Valyl-tRNA synthetase Heat-shock proteins Tumor necrosis factors alpha and beta

TAP and LMP Proteins

Class III (but encoded in Class II region) TAP-1 and TAP-2
Peptide transporter proteins Involved in Class I antigen processing

LMP-2 and LMP-7

Proteosome components Involved in Class I antigen processing

Class IV (Class I-Like) MHC Proteins

Structural similarities with Class I proteins Associated with beta-2 microglobulin Limited role in antigen presentation

MHC

Genetics
MHC genes are codominantly expressed

Regulation of expression