Autoimmunity

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66083/1/j.1365-4362.1981.tb00393.x.pd

Somatic diversification of variable lymphocyte receptors in the agnathan sea lamprey

Although jawless vertebrates are apparently capable of adaptive immune responses, they have not been found to possess the recombinatorial antigen receptors shared by all jawed vertebrates. Our search for the phylogenetic roots of adaptive immunity in the lamprey has instead identified a new type of variable lymphocyte receptors (VLRs) composed of highly diverse leucine-rich repeats (LRR) sandwiched between amino- and carboxy-terminal LRRs. An invariant stalk region tethers the VLRs to the cell surface by means of a glycosyl-phosphatidyl-inositol anchor. To generate rearranged VLR genes of the diversity necessary for an anticipatory immune system, the single lamprey VLR locus contains a large bank of diverse LRR cassettes, available for insertion into an incomplete germline VLR gene. Individual lymphocytes express a uniquely rearranged VLR gene in monoallelic fashion. Different evolutionary strategies were thus used to generate highly diverse lymphocyte receptors through rearrangement of LRR modules in agnathans ( jawless fish) and of immunoglobulin gene segments in gnathostomes ( jawed vertebrates).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62870/1/nature02740.pd

Cell interactions in the immune response in vitro. VI. Mediation by T cell surface monomeric IgM.

The nature of the specific mediator of T/B lymphocyte cooperation was investigated by using biochemical and in vitro culture methods in parallel. By surface radioiodination of activated thymus cells it was found that the T cell component of cell interaction was an immunoglobulin which possessed a mobility on polyacrylamide gel electrophoresis consistent with a molecular weight of approximately 180,000. This molecule comprised of two polypeptide chains, with the electrophoretic mobility of light and μ chains. This monomeric IgM molecule had specificity for the activating antigen, and like the mediator of cell interaction, bound cytophilically to macrophages, but not to T or B lymphocytes. These studies extend previous work in which the mediator of cell cooperation was found, by the use of antisera to contain antigen, and κ and μ chain determinants. The binding of the T cell surface IgM to macrophages supports the concept that the final step of cell cooperation, the immunization of B cells occurs at the surface of macrophages, occurs via a lattice of antigenic determinants created by cytophilic T cell carrier antibody. © 1973

T-CELL RECEPTORS OF MAN AND MOUSE STUDIED WITH ANTIBODIES AGAINST SYNTHETIC PEPTIDES

We used polyclonal rabbit antibodies directed against synthetic peptides predicted from the gene sequence of the human T-cell receptor (TCR) beta-chain YT35 to study the antigen receptor on human helper T-cell leukemia lines and on normal mouse thymocytes. Antibodies were raised to peptides corresponding to joining segment (Jbeta) and to a conserved stretch of sequence around the first cysteine in the constant region (Cbeta). These peptides were selected on the basis of homology with corresponding segments of immunoglobulin light chains. The specificity of the antibodies was established using synthetic overlapping peptides that modelled the complete TCR beta-chain. Western blot analysis was performed against detergent lysates of T cells. Both of the antibodies reacted strongly with 2-3 polypeptides in the mass range 40-45 kDa in mouse and human cells. Clearance experiments using monoclonal antibodies against murine TCR alpha- and beta-chains and against human TCR beta-chain and immunoprecipitations with monoclonal antibody to the murine T3 complex established that these components represented the alpha/beta heterodimer. An additional component around 31 kDa was detected by anti-Jbeta antibodies in murine thymus extracts. The use of the affinity-purified antipeptide antibody in two-dimensional Western blot analyses allows the clear discrimination between the characteristic individual receptors of monoclonal neoplastic T cells and the polydisperse patterns representative of heterogeneous normal populations. Antigenic cross-reactions between T-cell receptor beta-chains of man and mouse observed with monoclonal antibodies and rabbit antisera to peptides are consistent with the homology in gene sequence between the two species