MHC I and II: Introduction and Loci to DQ8, DR3, DR4

Content August 26, 2025

Major Histocompatibility Complex I and II Overview

MHC is encoded by HLA genes. These complexes present antigen fragments to T cells and bind T-cell receptors (TCRs).

MHC I Loci

Loci: HLA-A, HLA-B, HLA-C. MHC I loci have 1 letter.

MHC II Loci

Loci: HLA-DP, HLA-DQ, HLA-DR. MHC II loci have 2 letters.

MHC I: Binding, Structure, and Associated Proteins

Binding: TCR and CD8

Structure: 1 long chain, 1 short chain

Associated Proteins: β₂-microglobulin

MHC II: Binding, Structure, and Associated Proteins

Binding: TCR and CD4

Structure: 2 equal-length chains (2 α, 2 β)

Associated Proteins: Invariant chain

MHC I: Expression, Function, and Antigen Loading

Expression: All nucleated cells, APCs, platelets (except RBCs)

Function: Present endogenous antigens (e.g., viral or cytosolic proteins) to CD8+ cytotoxic T cells

Antigen Loading: Antigen peptides loaded onto MHC I in RER after delivery via TAP (transporter associated with antigen processing)

MHC II: Expression, Function, and Antigen Loading

Expression: APCs

Function: Present exogenous antigens (e.g., bacterial proteins) to CD4+ helper T cells

Antigen Loading: Antigen loaded following release of invariant chain in an acidified endosome

MHC Class I Structure Diagram

#boundingbox

This diagram illustrates the structure of MHC Class I. It shows the peptide-binding groove at the top, formed by the alpha-1 and alpha-2 domains. The alpha-3 domain is associated with beta-2 microglobulin. The complex is embedded in the cell membrane, extending into the cytoplasm.

MHC Class II Structure Diagram

#boundingbox

This diagram illustrates the structure of MHC Class II. It shows the peptide-binding groove formed by the alpha-1 and beta-1 domains. The alpha-2 and beta-2 domains are also shown, with the complex embedded in the cell membrane and extending into the cytoplasm.

HLA Subtypes Associated with Diseases

HLA SUBTYPE	DISEASE	MNEMONIC
B27	Psoriatic arthritis, Ankylosing spondylitis, IBD-associated arthritis, Reactive arthritis	PAIR
B57	Abacavir hypersensitivity

More HLA Subtypes and Diseases

DQ2/DQ8	Celiac disease	I ate (8) too (2) much gluten at Dairy Queen
DR3	DM type 1, SLE, Graves disease, Hashimoto thyroiditis, Addison disease	DM type 1: HLA-3 and -4 (1 + 3 = 4) SL3 (SLE)
DR4	Rheumatoid arthritis, DM type 1, Addison disease	There are 4 walls in 1 “rheum” (room)