Question

Given that HLA class I and II molecules are both synthesized within the endoplasmic reticulum (ER), why are cytosolic (i.e. endogenous) antigens not loaded onto (or bound to) HLA class II molecules within the ER?

a. ER resident aminopeptidase (ERAP) cannot trim peptides sufficiently to fit into the restricted peptide binding site (8-11 amino acids) HLA class II

b. Invariant chain blocks peptide loading of HLA class II

c. Endogenous antigens have no transporter to move them into the ER

d. Beta 2 (B2) microglobulin removes CLIP from the peptide binding site only after the HLA class II translocates to the endosome

e. Peptides in the ER are too small to bind to HLA class II molecules

Answer 1

B) is the right answer because HLA class ll molecules are synthesised in the ER and to avoid clogging its binding groove prematurely in the ER with peptide derived from endogenously synthesised proteins ,a special trimeric protein called invariant chain associates with the peptide binding groove .As the HLA class ll molecules present exogenous antigens which bind with it in the endosomes after degradation of invariant chain in the endosome.