Autophagy in MHC class II antigen processing

Durable adaptive immunity is dependent upon CD4 T-cell recognition of MHC class II molecules that display peptides from exogenous and endogenous antigens. Endogenously expressed cytosolic and nuclear antigens access MHC class II by way of several intracellular autophagic routes. These pathways include macroautophagy, microautophagy and chaperone-mediated autophagy. Macroautophagy can deliver antigens into autophagosomes for processing by acidic proteases before MHC class II presentation. However, other endogenous antigens are processed by cytoplasmic proteases, yielding fragments that translocate via chaperone-mediated autophagy into the endosomal network to intersect MHC class II. Cross-talk between autophagy pathways, particularly in response to stress, appears to balance the relative efficiency of each pathway. This might limit redundancy, giving MHC class II broader access to antigens within intracellular compartments distinct from the endosomal network.