Direct antigen presentation by DC shapes the functional CD8(+) T-cell repertoire against the nuclear self-antigen La-SSB.
Controversy still surrounds the importance of cross-presentation versus endogenous or direct presentation of MHC-I restricted Ag in CD8(+) T-cell (T(CD8+)) immunity. It is even less clear what relative role these pathways play in shaping the T-cell repertoire specific for ubiquitous self-antigens, especially in cases where both Ag presentation pathways could potentially be involved. Here we provide evidence that a T(CD8+) repertoire specific for a determinant from the nuclear autoantigen La-SSB is largely shaped by direct presentation. In this system, mouse T(CD8+) reactive to a xenogeneic human La (hLa(51-58)) K(b) peptide did not recognize directly presented peptide on either spleen cells from hLa-Tg mice or hLa transfected syngeneic cells. Interestingly, the same T(CD8+) were activated by in vivo challenge with allogeneic APC expressing either the Tg hLa or loaded with intact recombinant hLa protein, indicating functional cross-presentation of the hLa(51-58). However, in irradiated bone marrow chimeric mice, DC expressing Tg hLa, but not WT DC that matured in hLa-Tg mice, constitutively presented the hLa(51-58) to T(CD8+). These data demonstrate that although both the direct- and cross-presentation pathways are potentially operative in revealing hLa(51-58) to T(CD8+), the T(CD8+) repertoire to this determinant is shaped quantitatively according to the efficiency of Ag presentation.
Keech
Catherine L
CL
Department of Microbiology and Immunology, University of Melbourne, Victoria, Australia.
Pang
Ken C
KC
McCluskey
James
J
Chen
Weisan
W
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D001324:Autoantigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D045142:Cross-Priming / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006183:H-2 Antigens / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D012261:Ribonucleoproteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D000097585:SS-B Antigen
D001324:Autoantigens; D006183:H-2 Antigens; D012261:Ribonucleoproteins; D000097585:SS-B Antigen; C032876:H-2Kb protein, mouse