The outer surface lipoprotein A of Borrelia burgdorferi provides direct and indirect augmenting/co-stimulatory signals for the activation of CD4 super(+) and CD8 super(+) T cells

Naive CD4 super(+) and CD8 super(+) T cells require two distinct signals to proliferate and to express effector functions. One is provided by the antigen receptor on the T cell (TCR) after its encounter with antigenic peptides associated with class I or II major histocompatibility complex (MHC) molecules on antigen-presenting cells (APC). The second signal, which is not antigen-specific but essential for proliferation and differentiation of naive T cells, is provided by co-stimulatory structures. The major co-stimulatory molecules for CD4 super(+) T cells seem to be B7, B7.2, and heat-stable antigen (HSA). These molecules are expressed on a variety of native and/or activated APC and bind to CD28 and CTLA-4 and possibly other, as yet undefined, TCRs. Optimal T cell activation only occurs when co-stimulatory molecules and ligands for the TCR are expressed on the same APC. However, co-stimulation for T cells may also be provided via bystander cells or by glycoproteins of the extracellular matrix, like fibronectin and laminin. In this case, T-cell VLA integrins function as signaling molecules. This indicates that antigen-specific T-cell activation may also occur in areas where antigens are presented in association with extracellular matrix proteins. The recent finding that the invasion protein of Yersinia spp. delivers co-stimulatory signals to anti-CD3-activated human T cells, most probably through the b1 integrins, suggests that bacterial products can also bind to contribute to the activation of T cells. This points to another facet of bacteria-mediated lymphocyte activation, which may have important implications for the pathogenesis of infectious diseases.