REGULATION OF MUCOSAL IMMUNE RESPONSES IN HUMANS AND NON-HUMAN PRIMATES

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In these studies we are defining the role of the LAM-1 adhesion (MEL-14 lymph node homing receptor) molecule in T cell and B cell function. In preliminary studies, we determined that anti-LAM-1 antibodies can augment anti-CD3-induced proliferation of purified T cells. In further studies we immunoprecipitated surface radioiodinated T cell lysates with anti-CD3 and anti-LAM-1 mAb to determine if molecules in the TCR/CD3 complex associate with Leu 8 molecules. Although Leu 8 mAb immunoprecipitated only a single protein of approximately 80 kDa from T cell lysates treated with Nonidet P-40 under reducing condition, it coimmunoprecipitated additional proteins of 48, 42, 28, 24, and 22 kDa from T cell lysates treated with 3-[(3- cholamidopropyl)-dimethylammonio]-1-propanesulfonate (CHAPS). These additional proteins were identified as the alpha-, beta-, gamma-, delta-, and epsilon-chains of the TCR/CD3 complex by one-dimensional and two- dimensional diagonal SDS-PAGE. Densitometric scanning showed that, on average, 18% of the TCR/CD3 complex associates with LAM-1. In a final study, we showed by immunoblotting anlaysis using anti- peptide antibody that anti-LAM-1 mAb coimmunoprecipitates the chain of CD3. These results indicate that the human-lymph node homing receptor homologue (LAM- 1) participates in the activation of T cells, probably via its association with the TCR/CD3 complex.