Partial agonism elicits an enduring phase of T-cell-medicated antigen presentation.
Previous studies have shown that the anti-CD4 mAb W3/25 strongly enhances T cell APC (T-APC) activity. In this study, single positive CD4+ and double negative (DN) (CD4-CD8-) T-helper cells specific for the 55-69 or 72-86 sequence of guinea pig (GP) myelin basic protein (GPMBP) were used to study CD4 regulation of T-APC activity. Clones were cultured with irradiated SPL and GPMBP or rat (R) MBP for 2-3 days, were propagated in IL-2 for another 1-3 days, were irradiated, and were used as T-APC. DN T cells specific for GP55-69 effectively presented GPMBP and were superior APC compared to other CD4+ T cells for presentation of this antigen. In contrast, DN T cells specific for the dominant encephalitogenic 72-86 determinant did not effectively present the agonist GPMBP but potently presented the partial agonist RMBP. The heightened APC activity of DN T cells reflected the lack of CD4 because the anti-CD4 mAb W3/25 promoted T-APC activity of CD4+ T cells to those levels expressed by DN T cells. Overall, T cells with potent reactivity to GPMBP or RMBP were subsequently unable to present that antigen, whereas T cells exhibiting partial or low antigen reactivities were highly effective APC for presentation of that antigen. The unrelated antigen conalbumin was presented by MBP-specific clones only when added to culture with a specific partial agonist. Together, these data indicate that partially agonistic MHC ligands promote prolonged expression of T-APC activity and that DN T cells may be specialized to mediate postactivational antigen presentation.
Mannie
M D
MD
Department of Microbiology and Immunology, East Carolina University of Medicine, Greenville, North Carolina 27858-4354, USA. mannie@brody.med.ecu.edu
White
G A
GA
Nardella
J P
JP
Davidian
D K
DK
Arnold
P Y
PY
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D015704:CD4 Antigens / Q000096:biosynthesis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018956:CD5 Antigens / Q000096:biosynthesis; D002460:Cell Line; D006168:Guinea Pigs; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew
D015704:CD4 Antigens; D018956:CD5 Antigens; D004676:Myelin Basic Protein