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S M Behar

Publications and source records attributed to S M Behar.

25 records · Page 2Linked to original sources
PubMed1994

Recognition of a lipid antigen by CD1-restricted alpha beta+ T cells.

Major histocompatibility complex (MHC) class I and class II molecules bind immunogenic peptides and present them to lymphocytes bearing the alpha beta T-cell antigen receptor (TCR). An analogous antigen-presenting function also has been proposed for the non-MHC-encoded CD1 molecules, a family of non-polymorphic, beta 2-microglobulin-associated glycoproteins expressed on most professional antigen-presenting cells. In support of this hypothesis, CD1 molecules are recognized by selected CD4-CD8- alpha beta or gamma delta TCR+ T-cell clones, and we have recently shown that CD1 molecules restrict the recognition of foreign microbial antigens by alpha beta TCR+ T cells. But the substantial structural divergence of CD1 from MHC class I and class II molecules, raises the possibility that the antigens presented by the CD1 system may differ fundamentally from those presented by MHC-encoded molecules. Here we report that a purified CD1b-restricted antigen of Mycobacterium tuberculosis presented to alpha beta TCR+ T cells is mycolic acid, a family of alpha-branched, beta-hydroxy, long-chain fatty acids found in mycobacteria. This example of non-protein microbial antigen recognition suggests that alpha beta TCR+ T cells recognize a broader range of antigens than previously appreciated and that at least one member of the CD1 family has evolved the ability to present lipid antigens.

Antigen Presentation↗
PubMed1991

Characterization of somatically mutated S107 VH11-encoded anti-DNA autoantibodies derived from autoimmune (NZB x NZW)F1 mice.

We have studied 19 S107 heavy chain variable region gene (VH11)-encoded monoclonal antibodies from NZBWF1 mice. These studies show that a single VH gene can encode both antibodies to foreign antigens (anti-phosphorylcholine) and to self antigens (anti-double-stranded DNA) in the same animal. All of the anti-DNA antibodies contain many somatic mutations compared with the relevant germline genes. Since the anti-DNA antibodies were extensively somatically mutated and had undergone isotype switching, the response seems to be T cell dependent. While some of the antibodies appear to be the products of an antigen-driven and antigen-selected response, a number of characteristics of the antibodies suggest that forces other than antigen are contributing to the stimulation and selection of this response.

Amino Acid Sequence↗
PubMed1989

The molecular origin of anti-DNA antibodies.

The in vitro observation that a single point mutation in the protective anti-phosphorylcholine anti-bacterial antibody, S107, converts it into an autoantibody that reacts with dsDNA has focused our attention on the role of somatic mutation in generating autoantibodies. It has also led us to examine the significance of an individual's prior response to environmental antigens on the subsequent production of autoantibodies. The fact that genes of the S107 heavy chain variable region family could encode autoantibodies made it possible to clone and sequence the relevant germline genes of this small family from autoimmune (NZB x NZW)F1 mice and to compare these to the comparable genes in non-autoimmune mice. The germline genes from the normal and autoimmune mice are quite homologous and the small number of polymorphisms are not likely to predispose the autoimmune mice to the production of autoantibodies. (NZB x NZW)F1 mice respond to immunization with phosphorylcholine with a response that is largely encoded by the VH1 gene of the S107 family. However, when these same mice begin to make autoantibodies, their anti-DNA antibodies which are encoded by this family are in fact derived from the VH11 gene. The VH11 encoded anti-DNA antibodies which have been sequenced are all of the IgG2a subclass, react with dsDNA, and have undergone significant somatic diversification from the germline gene. Analysis of the ratio and location of the replacement and silent mutations suggests that the regulation of the autoantibody response differs from that of the normal response to foreign antigens. Our studies suggest that the utilization of a particular VH germline gene in the immune response to foreign antigens early in life does not lead to the preferential utilization of that same gene in the subsequent production of autoantibodies.

Amino Acid Sequence↗
PubMed1988

Somatic diversification of the S107 (T15) VH11 germ-line gene that encodes the heavy-chain variable region of antibodies to double-stranded DNA in (NZB x NZW)F1 mice.

A variety of studies suggest that members of the S107 (T15) heavy-chain variable-region gene family contribute to the autoimmune response of mice and humans to DNA. To identify the germ-line gene(s) involved and the degree of somatic diversification that occurs in such autoantibodies, we determined the mRNA sequence of the heavy and light chains of a group of monoclonal anti-DNA antibodies encoded by the S107 VH11 germ-line gene in (NZB x NZW)F1 mice. We also cloned and sequenced the VH11 germ-line gene of the NZB and NZW parental strains. The VH11 coding sequences of the two strains were identical. Comparison with this heavy-chain germ-line sequence showed that the variable regions of the monoclonal antibodies had undergone considerable somatic diversification.

Animals↗
PubMed1987

Studies on the somatic instability of immunoglobulin genes in vivo and in cultured cells.

We have examined the molecular mechanism and impact of somatic diversification on the T15 heavy chain variable region gene in vivo and in vitro. Somatic point mutation appears to be responsible for the changes we have observed in both hybridomas from early and late in the immune response and in the S107 myeloma cell line in culture. By identifying S107 mutants with decreases in antigen binding, we have shown that a single point mutation can cause the loss of binding to the eliciting antigen and the acquisition of binding to another antigen. Furthermore, in this case a point mutation of the T15 heavy chain variable region gene caused the conversion of an important protective antibody to an autoantibody. While the S107 cell line frequently generates both constant and variable region mutants, hybridomas appear to have relatively stable variable region genes and unstable constant region genes which in some cases result in mutants with increased binding.

Animals↗