CD4+ class I-restricted T cells specific for HIV gp160 315-329

Area of Science:

• Immunology
• T cell biology
• MHC restriction

Background:

• Mature T cells typically express either CD4 or CD8, with CD4+ T cells recognizing antigens with class II MHC and CD8+ T cells with class I MHC.
• The standard model of T cell recognition involves specific interactions between T cell receptors, antigens, and MHC molecules.

Purpose of the Study:

• To describe CD4+ T cell clones restricted to class I MHC molecules.
• To investigate the mechanisms by which CD4+ T cells could become restricted to class I MHC.

Main Methods:

• Generation and characterization of CD4+ T cell hybridomas and normal clones specific for HIV gp160 peptide 315-329 in association with H-2Dd.
• Determination of secondary antigen specificity for T cell clones to distinguish between thymic selection models.
• Functional assays using anti-CD4 monoclonal antibodies (mAbs) to assess T cell proliferation and signaling.

Main Results:

• Identification of CD4+ T cell clones recognizing HIV gp160 peptide 315-329 presented by the class I MHC molecule H-2Dd.
• Evidence suggesting normal thymic selection on class I MHC for some CD4+ clones, indicated by recognition of H-2Kk alloantigen.
• Inhibition of proliferation by anti-CD4 mAb, suggesting functional CD4 expression but also potential negative signaling.

Conclusions:

• CD4+ T cells can exhibit class I MHC restriction, expanding the known repertoire of T cell recognition.
• Two models are proposed: aberrant thymic selection on class I MHC or cross-reactive recognition involving both class I and class II MHC.
• Further investigation is needed to fully elucidate the developmental pathways and functional implications of CD4+ class I-restricted T cells.