Question

The peptide binding site on class I MHC molecules for presenting processed antigen to CD8 T cells is formed by:

• A. Proximal domain of the alpha subunit
• B. Distal domains of the alpha subunit
• C. Proximal domains of the alpha and beta subunits
• D. Distal domains of the alpha and beta subunits

Hint:

Class I groove is alpha1 plus alpha2, both distal domains of the same alpha chain.

Answer 1

The Correct Option is B

Step 1: MHC class I molecules present endogenous peptides to CD8 positive cytotoxic T cells. The structure has one polymorphic alpha chain with three domains, alpha1, alpha2 and alpha3, plus a non polymorphic beta2 microglobulin chain.
Step 2: The peptide binding groove of MHC class I is formed by the alpha1 and alpha2 domains. These are the membrane distal domains of the alpha chain, sitting farthest from the cell surface.
Step 3: The alpha3 domain is membrane proximal and is the one that interacts with the CD8 co receptor. Beta2 microglobulin only stabilizes the molecule and does not form the groove.
Step 4: So the binding site is built only by distal domains of the alpha chain. Option B describes the distal domains of the alpha subunit, which is correct.
Step 5: Why the others are wrong. Option A, a single proximal domain, is the alpha3 region, which binds CD8, not peptide. Options C and D wrongly bring in the beta chain, but in class I the beta chain is beta2 microglobulin and it does not contribute to the groove. The combined alpha plus beta groove description fits MHC class II, not class I.
Conclusion: The peptide binding site is formed by the distal domains of the alpha subunit, option B.