Q78. MHC-I groove can be loaded with peptides of only 8–10 amino acids because
- MHC-I groove is closed on both ends
- Fragments of only 8–10 amino acids are generated in MHC-I bearing cells
- β₂-microglobulin of MHC-I prevents the binding of large peptides to MHC-I
- β polypeptides of MHC-I prevent binding of 8–10 amino acid long peptides to MHC-I
MHC class I molecules bind peptides of 8–10 amino acids due to their closed-end binding groove structure. This prevents longer peptides from fitting properly.
Correct Answer
MHC-I groove is closed on both ends
The peptide-binding cleft in MHC class I (MHC-I) molecules forms a closed groove, with conserved residues like Tyr84 and Trp167 sealing the N- and C-terminal pockets (A and F pockets). This anchors the peptide ends via hydrogen bonds, restricting lengths to 8–10 amino acids (typically 9-mers), as longer peptides cannot fit without bulging or distortion. In contrast, MHC-II has open ends for longer peptides (13–25 residues).
Option Analysis
Option A: MHC-I Groove Closed on Both Ends
Correct. The closed structure pins peptide termini, limiting size to 8–10 residues for stable binding and T-cell recognition.
Option B: Fragments of Only 8–10 Amino Acids Generated
Incorrect. Proteasomes generate varied lengths (6–30+ residues), but only 8–10 fit MHC-I groove; longer ones trim or exclude.
Option C: β₂-Microglobulin Prevents Large Peptides
Incorrect. β₂-microglobulin stabilizes MHC-I but does not regulate peptide length; it aids folding and surface expression.
Option D: β Polypeptides Prevent 8–10 Amino Acid Binding
Incorrect. MHC-I has no “β polypeptides” (that’s MHC-II α/β); the α-chain forms the groove, and this option misstates prevention (it enables short peptides).
MHC-I Structure Basics
MHC-I comprises a heavy α-chain (domains α1-α3) non-covalently bound to β₂-microglobulin. The α1-α2 platform creates the groove for cytosolic peptide loading via TAP transporter. This ensures CD8+ T cells detect intracellular pathogens or anomalies.
