Mutations affecting antigen processing impair class II-restricted allorecognition.
Both exogenously derived and endogenously derived Ag generally require processing for their optimal binding and presentation by class I and class II major histocompatibility proteins. It is not known whether steps involved in Ag processing also affect the recognition of alloreactive T cells. We have recently described B cell mutants which have general defects in the processing and presentation of a variety of exogenous Ag to class II restricted T cells. In this report we have studied the ability of these processing mutants to stimulate a set of anti-DR3-specific alloreactive T cells clones. These processing/presentation mutants express normal MHC class II molecules, both in terms of primary sequence and cell surface abundance, but they appear unable to generate effective peptide-MHC complexes. When tested for their ability to stimulate MHC class II alloreactive T cell clones, only one of four T cell clones was stimulated by these mutants; the other three alloreactive T cell clones were not stimulated by either of two different mutants. Both of these mutants express normal levels of the accessory molecules, LFA-3 and ICAM-1. The inability of these mutants to stimulate three of four alloreactive clones indicates that the capacity to be recognized by many alloreactive T cells is linked to the Ag processing capacity of a stimulator cell.
Cotner
T
T
Department of Pediatrics, University of Washington, Seattle 98195.
Mellins
E
E
Johnson
A H
AH
Pious
D
D
D000938:Antigen-Presenting Cells / Q000276:immunology*; D000941:Antigens / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D002999:Clone Cells; D006681:HLA-D Antigens / Q000276:immunology*; D015803:HLA-DR3 Antigen / Q000276:immunology; D006801:Humans; D007109:Immunity / Q000235:genetics*; D009154:Mutation; D013601:T-Lymphocytes / Q000276:immunology
D000941:Antigens; D006681:HLA-D Antigens; D015803:HLA-DR3 Antigen