ABSTRACT
The immune system needs to recognise target protein antigens from pathogens residing in both extracellular and intracellular locations. Intricate proteolytic processing events that follow antigen/ pathogen encounter provide the immune system with a complex display of a heterogeneous peptide mix, instrumental in the initiation of T cell immune responses, and allow the separation of extracellular and intracellular pathogen identification. However, recent evidence shows that this conventional dimorphism in the proteolytic processing of endogenous versus internalised antigen is less restrictive than originally recognized. The events that constitute the conventional major histocompatibility complex (MHC)-restricted processing pathways are accompanied by interesting deviations that provide novel adjuncts for the processing machinery to gain access to antigen in varied intracellular locations. This review discusses these aspects of classical and non-classical processing pathways for MHC-restricted protein presentation, which play significant roles in both optimising and diversifying the peptide repertoire available for immune recognition.