Crystal structure of the human p58 killer cell inhibitory receptor (KIR2DL3) specific for HLA-Cw3-related MHC class I

AbstractBackground: T cells and natural killer (NK) cells perform complementary roles in the cellular immune system. T cells identify infected cells directly through recognition of antigenic peptides that are displayed at the target cell surface by the classical major histocompatibility complex (MHC) class I molecules. NK cells monitor the target cell surface for malfunction of this display system, lysing potentially infected cells that might otherwise evade recognition by the T cells. Human killer cell inhibitory receptors (KIRs) control this process by either inhibiting or activating the cytotoxic activity of NK cells via specific binding to MHC class I molecules on the target cell.Results: We report the crystal structure of the extracellular region of the human p58 KIR (KIR2DL3), which is specific for the human MHC class I molecule HLA-Cw3 and related alleles. The structure shows the predicted topology of two tandem immunoglobulin-like domains, but comparison with the previously reported structure of the related receptor KIR2DL1 reveals an unexpected change of 23° in the relative orientation of these domains.Conclusions: The altered orientation of the immunoglobulin-like domains maintains an unusually acute interdomain elbow angle, which therefore appears to be a distinctive feature of the KIRs. The putative MHC class I binding site is located on the outer surface of the elbow, spanning both domains. The unexpected observation that this binding site can be modulated by differences in the relative domain orientations has implications for the general mechanism of KIR–MHC class I complex formation

HLA and human mate choice: tests on Japanese couples

Abstract House mice are apparently more likely to mate with individuals dissimilar to themselves at MHC (major histocompatibility complex) loci than with similar individuals. Such negative assortative mating is thought to be mediated by olfaction. Recently, it has been suggested that human mate choice may be affected by HLA (human leukocyte antigen; MHC in humans), based on the finding that women prefer the odor of men dissimilar to themselves at HLA loci to that of HLA-similar men. If these odor preferences are indeed an important criterion of mate choice in humans, actual marriages may show negative assortment with respect to HLA. In this paper, we compared the observed similarity between spouses at HLA loci with the expected similarity under random mating, for about 150 couples from 6 prefectures in the Tohoku region of Japan, and for about 300 couples from 16 prefectures all over Japan. For statistical tests, we used empirical distributions of goodness-of-fit statistics, X 2 and G, obtained by Monte Carlo methods, because these statistics may not follow the chi-square distribution. Tests for each sample as a whole and for each prefecture rule out strong disassortative mating at the HLA-A and HLA-C loci

HLA and anti-GQ1b IgG antibody in Miller Fisher syndrome and Guillain-Barré syndrome

We investigated serological human leukocyte antigen (HLA) types in patients with histories of Miller Fisher syndrome (MFS) and Guillain-Barré syndrome (GBS) with ophthalmoplegia, in whom serum anti-GQ1b IgG antibody was present during the acute phase. We examined class I antigens (A, B and C) in 32 patients and class II antigens (DR and DQ) in 30, but found no association. We conclude that particular serologically defined HLA types are not preferred for the immunoresponse of anti-GQ1b IgG antibody in MFS and GBS

Detection of Antilymphocyte Antibody with Two-Color Method in Systemic Lupus Erythematosus and Its Heterogeneous Specificities against Human T-Cell Subsets

The two-color method originally described by Van Rood et al. (Van Rood, J. J., A. Van Leeuwen, and J. S. Ploen. 1976. Simultaneous detection of two cell populations by two-color fluorescence and application to the recognition of B-cell determinants. Nature (Lond.). 262: 795-797) for the typing of homologous leukocytic antibodies, D-region was used for the detection of antilymphocyte antibody (ALA) in systemic lupus erythematosus. In this method, surface immunoglobulin-bearing cells were identified with fluorescein isothiocyanate-labeled anti-immunoglobulin and nuclei of killed cells were stained with ethidium bromide. Therefore, cell type (T or B) of the target cells can be identified without fractionating them. ALA was detected in 87% of lupus sera and had a preferential reactivity with T cells. Its major immunoglobulin class was shown to be immunoglobulin (Ig)M. The subspecificity of ALA was further analyzed using fractionated T-cell subsets as target cells. When T lymphocytes were separated into Fc receptor-bearing (Tγ) and lacking (Tγ[-]) cells, 64% of ALA showed preferential reactivity with Tγ cells and 14% with Tγ(-) cells. The remainder had no selective reactivity against Tγ or Tγ(-) cells. Tγ cells were shown to have suppressor activity, whereas Tγ(-) cells were indicated to contain helper cells. The above finding was in agreement with the observation that treatment of T cells with ALA that preferentially react with Tγ cells considerably enhanced immunoglobulin synthesis in vitro, whereas treatment of T cells with ALA reactive with Tγ(-) cells clearly suppressed the formation of immunoglobulins. Treatment of ALA with no selective reactivity showed variable effects on in vitro immunoglobulin synthesis. These results indicate that ALA in lupus have heterogeneous specificities against human T-cell subsets