Genetically encoded and post-translationally modified forms of a major histocompatibility complex class I-restricted antigen bearing a glycosylation motif are independently processed and co-presented to cytotoxic T lymphocytes.
The mechanisms by which antigenic peptides bearing a glycosylation site may be processed from viral glycoproteins, post-translationally modified, and presented by major histocompatibility complex class I molecules remain poorly understood. With the aim of exploring these processes, we have dissected the structural and functional properties of the MHC-restricted peptide GP92-101 (CSANNSHHYI) generated from the lymphocytic choriomeningitis virus (LCMV) GP1 glycoprotein. LCMV GP92-101 bears a glycosylation motif -NXS- that is naturally N-glycosylated in the mature viral glycoprotein, displays high affinity for H-2D(b) molecules, and elicits a CD8(+) cytotoxic T lymphocyte response. By analyzing the functional properties of natural and synthetic peptides and by identifying the viral sequence(s) from the pool of naturally occurring peptides, we demonstrated that multiple forms of LCMV GP92-101 were generated from the viral glycoprotein and co-presented at the surface of LCMV-infected cells. They corresponded to non-glycosylated and post-translationally modified sequences (conversion of Asn-95 to Asp or alteration of Cys-92). The glycosylated form, despite its potential immunogenicity, was not detected. These data illustrate that distinct, non-mutually exclusive antigen presentation pathways may occur simultaneously within a cell to generate structurally and functionally different peptides from a single genetically encoded sequence, thus contributing to increasing the diversity of the T cell repertoire.
Hudrisier
D
D
Institut de Pharmacologie et de Biologie Structurale, UPR 9062 CNRS, 205 route de Narbonne, 31400 Toulouse, France. hudrisie@ipbs.fr
Riond
J
J
Mazarguil
H
H
Oldstone
M B
MB
Gairin
J E
JE
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics* / Q000276:immunology; D002478:Cells, Cultured; D006031:Glycosylation; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D011499:Protein Processing, Post-Translational / Q000235:genetics* / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D015395:Histocompatibility Antigens Class I