Recognition of pre-processed endogenous antigen by class I but not class II MHC-restricted T cells

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Abstract
CLASS I and class II MHC-restricted T lymphocytes recognize non-native forms of antigen1–7. The presentation of antigen to these two classes of T lymphocytes can occur through distinct pathways8–10. Several mechanisms, including differences in antigen processing in different intracellular compartments, have been proposed to account for these pathway differences9–14. Here we describe a T-cell epitope located on the influenza virus haemag-glutinin, which is recognized by both class I and class II MHC-restricted cytolytic T lymphocytes (CTL). When expressed de novo in target cells, from a synthetic minigene15 encoding only the epitope, this pre-processed antigenic site is recognized by class I but not class II MHC-restricted T lymphocytes, even though target cells treated with the exogenously introduced peptide can be recognized by both classes of T cells. Because endogenous expression of the pre-processed antigenic fragment results in differential presentation to class I and class II MHC-restricted CTL, differences between the two different pathways of presentation could lie not at the level of processing but at the level of targeting and/or interaction of processed antigen with MHC.

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