LFA-1 and other accessory molecules functioning in adhesions of T and B lymphocytes

摘要: Abstract Adhesions of lymphocytes, among themselves or with other cell types, are necessary for most steps in immune responses including both induction and effector phases. Among adhesions T cells involving specific immunological recognition, CTL-target have been the studied. Although CTL-mediated killing is highly (specific/nonspecific lytic activity 50-fold), adhesion (conjugation) less so. In mouse, specificity conjugation has typically four to eightfold. Two recent studies cloned human CTL found much conjugation, from onefold (no specificity) 1.5-fold. Thus, CTL, may occur promiscuously any potential target; recognition following lethal hit delivery. The fact that antibodies antigen receptor (Ti CD3) inhibit without inhibiting supports this view. ability lymphocytes form nonspecific adhesions, plus dependence even mouse on temperature, metabolic energy, magnesium, a an intact cytoskeleton suggest bulk strength lymphocyte not simply sum bonds between receptors (Ti) antigen. Lymphocytes evidently possess separate “adhesion strengthening” mechanisms. similarities properties antigen-independent homotypic B (Table 2) at least some these mechanisms widely used hematopoetic origin. MoAbs surface molecules, when bound living membrane, no evident functional effects function. However, minority can either activate functions. Such identify “leukocyte (or lymphocyte) function-associated antigens,” LFAs (not all which happen “LFA” their names, Table 1). Most inhibitory appears account functions such as proliferation. binding particular membrane glycoprotein inhibits does guarantee question direct participant (one “glue” molecules). there scanty evidence support indirect “negative signals” be induced by antibodies, participation seems likely. LFA-1 adhesion-blocking site expressed only cells: anti-LFA-1 CTL- NK-target activated lymphocyte-endothelium adhesion, neutrophil monocyte adhesions. Cells patients deficient show defective adhesion. prime candidate molecule. Since antibody + − cells, molecule bind opposing must something distinct LFA-1. This hypothetical counterstructure remains identified. At present, T-lymphocyte appear likely involve five molecularly 3). Antigen-independent (i) its counterstructure; (ii) CD8 CD4 perhaps conserved regions class I II HLA respectively; (iii) CD2 (the sheep red receptor, T11, LFA-2) counterstructure, LFA-3. endothelium involve, addition, (iv) counterpart MEL-14 lymph node peyer's patch-specific (HEBF). Finally, antigen-bearing (v) antigen-specific Ti/CD3 HLA. latter interaction provide one weakest components regulation interactions various molecules (and consequently function) will fascinating subject future work. Anti-LFA-1 profoundly adhesion-dependent tested vitro. model, was more immunosuppressive vivo than were antigens. major component classical anti-lymphocyte serum, promise becoming useful therapeutic tool clinic.