Studies on murine T cells: Recognition of HIVgp160 315-329 and response to costimulation

Abstract

We have examined various aspects of murine T cell physiology. First, we have examined the ability of T cells induced with a peptide antigen to recognize whole molecule and lipopeptide antigen constructs. Mice were primed with peptide 315-329 from human immunodeficiency virus (HIV) gp160 strain IIIb in complete Freund's adjuvant. Splenocytes from these peptide primed mice contained both class I- and class II-restricted T cells. Both the class I- and class II-restricted cells failed to recognize lipopeptide antigens suggesting that lipidation of a peptide antigen does not always increase its antigenicity. Some of the peptide induced T cells were capable of recognizing Baculovirus derived HIV gp120. However, at least some class II-restricted peptide induced T cells did not recognize gp120, suggesting that at least some class II-restricted determinants may not be generated from the whole molecule by processing in vivo. Second, we have identified CD4{dollar}\sp+{dollar} class I-restricted T cells in splenocytes from mice primed as described above. These T cells represent an exception to the usual correlation of CD4 expression with class II-restriction in mature T cells. We found that the CD4{dollar}\sp+{dollar} class I-restricted T cells recognized a class I alloantigen and thus either were selected extrathymically or were selected on class I major histocompatibility complex antigens in the thymus. Third, we have examined the role of costimulation in the activation of T cell hybridomas. T cell hybridomas are thought not to require accessory cell (AC) derived costimulatory signals for activation. Using T cell hybridomas stimulated with immobilized anti-CD3 antibodies, we found that the activation of T cell hybridomas could be enhanced by AC derived signals. We also found that these signals were not mediated by soluble molecules and that there was considerable heterogeneity in both the delivery of and response to these costimulatory signals.