U01.02.007 Major histocompatibility complex I and II

The Major Histocompatibility Complex (MHC) plays a crucial role in the immune system by presenting antigen fragments to T cells and binding to T-cell receptors (TCRs). It is encoded by the human leukocyte antigen (HLA) genes and is divided into MHC class I and class II molecules.

Structure and Location

MHC Class I

Loci: HLA-A, HLA-B, HLA-C (MHC I loci have one letter)
Structure: One long chain and one short chain
Expression: Present on all nucleated cells, antigen-presenting cells (APCs), and platelets (except red blood cells)

MHC Class II

Loci: HLA-DP, HLA-DQ, HLA-DR (MHC II loci have two letters)
Structure: Two equal-length chains (2 α and 2 β chains)
Expression: Only on APCs (antigen-presenting cells)

Function and Antigen Presentation

MHC Class I

Function: Presents endogenous antigens (e.g., viral or cytosolic proteins) to CD8+ cytotoxic T cells.
Antigen Loading: Antigen peptides are loaded onto MHC I in the rough endoplasmic reticulum (RER) after delivery via TAP (transporter associated with antigen processing).
Associated Proteins: β2-microglobulin.

MHC Class II

Function: Presents exogenous antigens (e.g., bacterial proteins) to CD4+ helper T cells.
Antigen Loading: Antigens are loaded following the release of the invariant chain in an acidified endosome.
Associated Proteins: Invariant chain.

Binding to T-Cell Receptors

MHC Class I: Binds to TCR and CD8 receptors on cytotoxic T cells.
MHC Class II: Binds to TCR and CD4 receptors on helper T cells.

Comparison Table

Feature	MHC Class I	MHC Class II
Loci	HLA-A, HLA-B, HLA-C (1 letter)	HLA-DP, HLA-DQ, HLA-DR (2 letters)
Structure	1 long chain, 1 short chain	2 equal-length chains (2 α, 2 β)
Expression	All nucleated cells, APCs, platelets (not RBCs)	APCs only
Antigen Type	Endogenous antigens	Exogenous antigens
Present to	CD8+ cytotoxic T cells	CD4+ helper T cells
Antigen Loading	RER via TAP	Endosome after release of invariant chain
Associated Proteins	β2-microglobulin	Invariant chain

Comparison Table

Points to Remember

MHC molecules are crucial for T cell-mediated immune responses.
MHC Class I presents endogenous antigens to CD8+ T cells, while MHC Class II presents exogenous antigens to CD4+ T cells.
MHC I loci have one letter (HLA-A, HLA-B, HLA-C), while MHC II loci have two letters (HLA-DP, HLA-DQ, HLA-DR).
Antigen loading in MHC I occurs in the rough ER, whereas for MHC II, it happens in the endosome.

Bibliography

Janeway CA Jr, Travers P, Walport M, Shlomchik MJ. Immunobiology: The Immune System in Health and Disease. 5th edition. New York: Garland Science; 2001. Major Histocompatibility Complex.
Murphy K, Weaver C. Janeway’s Immunobiology. 9th ed. New York: Garland Science; 2016.
Parham P. The Immune System. 4th ed. New York: Garland Science; 2014.

USMLE Step 1 Review Series

Curriculum

U01.02.007 Major histocompatibility complex I and II

Structure and Location

MHC Class I

MHC Class II

Function and Antigen Presentation

MHC Class I

MHC Class II

Binding to T-Cell Receptors

Comparison Table

Points to Remember

Bibliography

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