Antigen cognate

This class of lymphocytes differentiates from immuno-logically incompetent hematopoietic stem cells of the bone marrow within the thymus - hence, the name thymus-dependent (T-) lymphocytes. Two major subclasses develop simultaneously, T-helper lymphocytes (Th) and cytotoxic effector lymphocytes (Tc). The cytotoxic T-lymphocytes (carrying on the surface the differentiation marker CD8) destroy cells, which cany their cognate antigen bound to MHC class I molecules on the surface by inducing apoptosis. From an evolutionary point of view Tc cells appear to have developed predominantly to cope with vims infections. As vituses can only replicate within cells, Tc eliminate them by destroying their producers. 

Pacholczyk R, Kern J, Singh N, Iwashima M, Kraj P, Ignatowicz L Nonself-antigens are the cognate specificities of Foxp3-H regulatory T cells. Immunity 2007 27 493-504. 

Polyclonal antisera are usually prepared either from isolated antigens, such as proteins or from synthetic peptides derived from the protein sequence. The antisera derived from small synthetic peptides are regio-specific with respect to the cognate protein and resemble in some way the monoclonal antibodies, but they are much easier to prepare. 

The affinities of antibodies for their cognate peptides can be very high, so it is sometimes difficult to recover quantitatively the higher-affinity antibodies in a polyclonal serum from the peptide resin. For this reason, it is essential to use only low concentrations of peptide on the resin (typically 100-200 pg of peptide/mL of agarose gel) and to elute bound antibody m the reverse direction to which it was run into the column, so as not to drive eluting antibodies into a further excess of antigen. If both of these criteria are adhered to, yields are usually on the order of 60-80% recovery. 

The final stage of B cell differentiation where the BCR repertoire is shaped is the germinal centre (GC) reaction. In the T cell dependent GC reaction, the BCR is adapted for its cognate antigen by somatic hypermutation (SMH) and class switch recombination (CSR), both of which are driven by activation induced cytidine deaminase (AID). Since AID induces targeted point mutations in the CDRs of the Ig HCs and Ig LCs, this can dramatically alter the BCR affinity or even its specificity. As AID activity may also result in the formation of an autoreactive BCR, a stringent counterselection of such self-reactive B cells is required. By analysis in human of the BCR repertoire of post-GC IgG+ memory B cells, it was demonstrated that indeed new auto-reactive B cells develop by SHM whereas 20% of naive B cells is self-reactive, up to 40% of the IgG+ memory B cells expressed a true de novo created self-reactive BCR. Apparently, lack of T cell help prevents activation of these self-... 

To counter the low success rate of B-cell epitope prediction, MHC class II epitopes for CD4+ T cells may be emphasized when antibody response is key in vaccine design. CD4+ T-helper cells are critical to induce the activation of B cells that produce antibodies. B-cell antigens that contain significant MHC class II epitopes may outperform B-cell antigens without cognate help. An identified T-cell epitope may sometimes contain a B-cell epitope. In addition, B-cell epitopes may colocalize near or overlap MHC class II epitopes (32, 33). 

Krebber C, Spada S, Desplancq D, Pluckthun A, Co-selection of cognate antibody antigen pairs by selectively-infective phages, FEBS Lett., 377 227-231,... 

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