Modulation of antigen presentation and peptide-MHC-specific, LFA-1-dependent T cell-macrophage adhesion.
Incubation of peritoneal macrophages in vitro before fixation increased their ability to present exogenous peptides to 3A9 T hybridoma cells. The enhanced level of presentation correlated with a greatly increased, peptide-specific adhesion of 3A9 cells to the macrophages, whereas peptide-independent adhesion was minimal and essentially unaltered. 3A9 cells exhibited rapid peptide-specific adhesion (plateau by 5 to 10 min) and deadhesion (complete reversal by 5 min). Peptide-specific adhesion was blocked by anti-I-Ak and anti-LFA-1. Interaction of T cell receptors and CD-4 with peptide-I-Ak complexes appeared to provide little direct contribution to the avidity of T cell-macrophage adhesion, but activated a LFA-1-mediated adhesion mechanism. In addition, anti-T cell receptor, anti-CD3, and anti-CD4 antibodies themselves activated LFA-1-dependent adhesion in the absence of peptide. Unlike the peptide-induced adhesion, this adhesion was similar for macrophages whether or not they were incubated in vitro before fixation. We conclude that the different macrophage populations supported LFA-1-mediated adhesion equally. Therefore, the enhancement of T cell stimulation observed after in vitro incubation of macrophages was due to increased peptide presentation and consequently increased triggering of LFA-1-mediated adhesion. Mechanisms may exist to regulate the effectiveness with which peptide-class II MHC complexes are displayed for T cell recognition.
Harding
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Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110.
Unanue
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D000818:Animals; D000918:Antibody Specificity; D000941:Antigens / Q000096:biosynthesis*; D015704:CD4 Antigens / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D006649:Histocompatibility Antigens / Q000502:physiology*; D006825:Hybridomas / Q000502:physiology; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008808:Mice, Inbred CBA; D011948:Receptors, Antigen, T-Cell / Q000502:physiology
D000941:Antigens; D015704:CD4 Antigens; D006649:Histocompatibility Antigens; D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1; D011948:Receptors, Antigen, T-Cell