MHC Class I and II Protein Structure and Function

Classical MHC class I and MHC class II molecules are both involved in antigen presentation to T cells but have distinct structures and functions. Here’s a comparison of their structures:

Classical MHC Class I Molecules

1. Structure:
   • MHC class I molecules are composed of a single polypeptide chain, typically referred to as the α chain, which is non-covalently associated with β2-microglobulin (β2m), a small protein.
   • The α chain consists of three extracellular domains: α1, α2, and α3. The α1 and α2 domains form a peptide-binding groove, where the antigenic peptide binds. The α3 domain interacts with CD8 molecules on cytotoxic T cells.
   • MHC class I molecules are anchored in the membrane of the presenting cell.
2. Function:
   • Classical MHC class I molecules present endogenous peptides derived from cytosolic proteins to CD8+ cytotoxic T cells.
   • These peptides are typically 8-10 amino acids in length and are derived from proteins that have been degraded by the proteasome.

Classical MHC Class II Molecules

1. Structure:
   • MHC class II molecules are composed of two polypeptide chains: an α chain and a β chain, both of which are encoded by genes within the MHC locus.
   • Each chain consists of two extracellular domains: α1 and α2 for the α chain, and β1 and β2 for the β chain. These domains form the peptide-binding groove.
   • Unlike MHC class I molecules, MHC class II molecules are anchored in the membrane of antigen-presenting cells.
2. Function:
   • Classical MHC class II molecules present exogenous peptides derived from extracellular proteins to CD4+ helper T cells.
   • These peptides are typically longer (around 13-25 amino acids) than those presented by MHC class I molecules and are derived from proteins that have been internalized by the antigen-presenting cell and processed in endosomes or lysosomes.

While both MHC class I and class II molecules are essential for adaptive immune responses, they differ in structure, composition, and the types of peptides they present to T cells.

Next Topic: Pros and Cons of MHC Polymorphisms

Source: ChatGPT response prompted and edited by Joel Graff.

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