R. M. Zinkernagel

Bio: R. M. Zinkernagel is an academic researcher from Australian National University. The author has contributed to research in topics: Lymphocytic choriomeningitis & Antigen. The author has an hindex of 8, co-authored 13 publications receiving 4315 citations.

Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system.

Abstract: RECENT experiments1–3 indicate that cooperation between thymus derived lymphocytes (T cells) and antibody-forming cell precursors (B cells) is restricted by the H-2 gene complex Helper activity in vivo operates only when T cells and B cells share at least one set of H-2 antigenic specificities Evidence is presented here that the interaction of cytotoxic T cells with other somatic cells budding4–5 lymphocytic choriomeningitis (LCM) virus is similarly restricted

Immunological surveillance against altered self components by sensitised T lymphocytes in lymphocytic choriomeningitis.

Abstract: THE cytotoxic activity1,2 of immune thymus-derived lymphocytes (T cells) for 51Cr-labelled fibroblasts, or macrophages infected with lymphocytic choriomeningitis (LCM) virus is restricted by the H-2 gene complex3,4. Specific lysis of LCM-infected monolayer cultures occurs only when targets and overlaying, sensitised T cells share at least one set of H-2 antigenic specificities.

Enhanced immunological surveillance in mice heterozygous at the H-2 gene complex.

Abstract: THE major histocompatibility (H) antigens of higher animals show extreme genetic polymorphism equalled, in higher vertebrates, only by that associated with the immunoglobulins1. Maintenance of such a high rate of variability implies evolutionary advantage for heterozygotes in the HL-A system for man, or at the H-2 gene complex in mice2,3. We propose a possible selective mechanism, based on the realisation that immunological surveillance function (defined here as recognition and elimination of modified host cells by sensitised thymus-derived lymphocytes (T-cells) may be considerably enhanced in mice heterozygous at the H-2 gene complex.

Genes required for cytotoxicity against virus-infected target cells in k and d regions of h-2 complex.

Abstract: EVIDENCE is mounting that in mice, certain specific immunological effector functions of thymus-derived (T) lymphocytes are efficient only when donors of T cells and the cells with which they interact have at least a part of the H-2 gene complex in common1–8. Examples include T helper function in vivo and in vitro1–3, cytotoxicity mediated by T cells against virus-infected4–6 or TNP-modified7 target cells in vitro, immunopathology mediated by T cells4, or protection against bacterial8 and viral infection6 in vivo. This requirement for H-2 compatibility has been studied in detail by measuring the cytotoxicity of T cells from donors immunised with either lymphocytic choriomeningitis (LCM) or ectromelia virus using target cells infected with the homologus virus.

Structure of the human class I histocompatibility antigen, HLA-A2.

Abstract: The class I histocompatibility antigen from human cell membranes has two structural motifs: the membrane-proximal end of the glycoprotein contains two domains with immunoglobulin-folds that are paired in a novel manner, and the region distal from the membrane is a platform of eight antiparallel beta-strands topped by alpha-helices. A large groove between the alpha-helices provides a binding site for processed foreign antigens. An unknown 'antigen' is found in this site in crystals of purified HLA-A2.

Biology of natural killer cells.

Abstract: Publisher Summary Studies of cytotoxicity by human lymphocytes revealed not only that both allogeneic and syngeneic tumor cells were lysed in a non-MHC-restricted fashion, but also that lymphocytes from normal donors were often cytotoxic. Lymphocytes from any healthy donor, as well as peripheral blood and spleen lymphocytes from several experimental animals, in the absence of known or deliberate sensitization, were found to be spontaneously cytotoxic in vitro for some normal fresh cells, most cultured cell lines, immature hematopoietic cells, and tumor cells. This type of nonadaptive, non-MHC-restricted cellmediated cytotoxicity was defined as “natural” cytotoxicity, and the effector cells mediating natural cytotoxicity were functionally defined as natural killer (NK) cells. The existence of NK cells has prompted a reinterpretation of both the studies of specific cytotoxicity against spontaneous human tumors and the theory of immune surveillance, at least in its most restrictive interpretation. Unlike cytotoxic T cells, NK cells cannot be demonstrated to have clonally distributed specificity, restriction for MHC products at the target cell surface, or immunological memory. NK cells cannot yet be formally assigned to a single lineage based on the definitive identification of a stem cell, a distinct anatomical location of maturation, or unique genotypic rearrangements.

T-cell antigen receptor genes and T-cell recognition.

Abstract: The four distinct T-cell antigen receptor polypeptides (alpha, beta, gamma, delta) form two different heterodimers (alpha:beta and gamma:delta) that are very similar to immunoglobulins in primary sequence, gene organization and modes of rearrangement. Whereas antibodies have both soluble and membrane forms that can bind to antigens alone, T-cell receptors exist only on cell surfaces and recognize antigen fragments only when they are embedded in major histocompatibility complex (MHC) molecules. Patterns of diversity in T-cell receptor genes together with structural features of immunoglobulin and MHC molecules suggest a model for how this recognition might occur. This view of T-cell recognition has implications for how the receptors might be selected in the thymus and how they (and immunoglobulins) may have arisen during evolution.

Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules.

Abstract: The crystal structures of major histocompatibility complex (MHC) molecules contain a groove occupied by heterogeneous material thought to represent peptides central to immune recognition, although until now relatively little characterization of the peptides has been possible. Exact information about the contents of MHC grooves is now provided. Moreover, each MHC class I allele has its individual rules to which peptides presented in the groove adhere.

The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens

Abstract: Most of the polymorphic amino acids of the class I histocompatibility antigen, HLA-A2, are clustered on top of the molecule in a large groove identified as the recognition site for processed foreign antigens. Many residues critical for T-cell recognition of HLA are located in this site, in positions allowing them to serve as ligands to processed antigens. These findings have implications for how the products of the major histocompatibility complex (MHC) recognize foreign antigens.