Partial agonism elicits an enduring phase of T-cell-medicated antigen presentation.

Abstract:

: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.

journal_name

Cell Immunol

journal_title

Cellular immunology

authors

Mannie MD,White GA,Nardella JP,Davidian DK,Arnold PY

doi

10.1006/cimm.1998.1299

subject

Has Abstract

pub_date

1998-06-15 00:00:00

pages

83-93

issue

2

eissn

0008-8749

issn

1090-2163

pii

S0008874998912990

journal_volume

186

pub_type

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