Abstract
Abstract Natural killer cell activity participates in the elimination of tumors and virus infections. Data presented here include their role in a virus infection (HIV), metastatic breast cancer, and aging per se. We have analyzed two gene segments MHC HLA class I ligands and NK receptors Each have single amino acid differences. Together these alleles can identify long term survivors. Homozygosity of HLA–Bw4 supertype in HIV progression has been described. Since HLA-KIR genetic interactions of HLA-Bw4 with KIR (3DS1) only included Bw4, with the exception of B*27 and B*44 that use different mechanism of protection, on the clinical outcome of HIV infection, NK–ligand interactions (NKG2A-HLA-E with HLA class I leader peptides) explain the long term non-progressors (LTNP) to AIDS. HLA-B alleles have Methionine (Met) or Threonine (Thr) at second position (P2) of their leader peptide. HLA-Bw4 alleles, with exception of B*38, encode leader peptide with Thr at P2 and HLA-Bw6 genes that encode Met at P2 are B*07, B*08 and B*14. All others have Thr at P2. Comparisons of the Thr in LTNP with progressors, up to 15 years. with non-infected Caucasian controls were significant. Also, aged Mexicans demonstrated significant increase of homozygosity of Thr at P2 and Mexican patients with metastatic breast cancer were studied 10 years after treatment with surgery and chemotherapy, The 39 survivors demonstrated significant increase of homozygosity of Thr at P2 compared to controls without cancer and the 37 non survivors. These findings need to be studied in different malignancies and different ethnicities as well as in mouse models. Our findings support the immunogenetic theory of cancer and aging.
Published Version
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