T Cell Regulatory Genes And Methods Of Use Thereof

Abstract

A genetic locus and corresponding family of proteins associated with regulation of immune function and cell survival are provided. These genes encode cell surface molecules with conserved IgV and mucin domains. The locus comprising the TIM family is genetically associated with immune dysfunction, including asthma. Furthermore, the TIM gene family is located within a region of human chromosome 5 that is commonly deleted in malignancies and myelodysplastic syndrome. Polymorphisms in the gene sequences are associated with the development of airway hyperreactivity and allergic inflammation, and T cell production of IL-4 and IL-13. The proteins include the human hepatitis A cellular receptor, hHAVcr-1.

Description

BACKGROUND OF THE INVENTION[0001]The astonishing complexity of the immune system is its greatest strength. The 1012-1014 possible antibody specificities, the delicate interplay between the various regulatory and effector cells, the restriction of T cell responses according to MHC antigens; all these contribute to the ability of the host to effectively react against infectious agents and other antigens perceived as foreign. But this diversity has its drawbacks. Mistakes happen: the target of a response may turn out to be a normal self protein; inflammatory responses are misregulated; and normal responses are undesirably directed against grafts and transplanted cells. Under these circumstances, the complexity of the system makes diagnosis and therapy extremely difficult.[0002]The profile of cytokines produced by CD4+ T cells during an immune response determines the nature of effector functions which develop and regulates the outcome of an immune response. Production of IL-2 and IFN-γ ...

AI Technical Summary

Problems solved by technology

The astonishing complexity of the immune system is its greatest strength.

But this diversity has its drawbacks.

Under these circumstances, the complexity of the system makes diagnosis and therapy extremely difficult.

Asthma is the most common chronic disease of childhood and affects more than 15 million individuals in the United States, leading to direct treatment costs exceeding $11 billion per annum.

However, the specific molecular pathways that result in the increased asthma prevalence, and the genetic polymorphisms that confer asthma susceptibility are poorly understood.

Moreover, because the effects of genetic variation in any single gene are likely to have only modest effects in the overall pathogenesis of asthma, and because gene-gene and gene-environment interactions confound the analysis, the location of putative susceptibility genes to regions amenable to positional cloning has proven difficult to refine.

However, the large size of the linked region of 5q complicates its analysis, and a gene for asthma from this site has not yet been conclusively identified.

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