Cell Mediated Lympholysis in Man. Patterns of Killing Power in Relation to the HL‐A System

Grunnet, Niels; Kristensen, Tom; Kissmeyer‐Nielsen, F.

doi:10.1111/j.1399-0039.1975.tb00635.x

Cited by 14 publications

(2 citation statements)

References 7 publications

(7 reference statements)

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“…Eijsvoogel et al (1973) suggested that the FOUR antigens were better target determinants than LA antigens. These findings, except for the general superiority of the FOUR antigens, have been confirmed in a compiled study involving 1,299 observations (Grunnet et al 1975b), but this study substantiated the existence of either a separate ICML locus or the varying strength of the LA and FOUR antigens. Since most experimental results could be interpreted meaningfully by introduction of the LA and FOUR antigens as sole target determinants, it is reasonable to map this hypothetical ICML locus inside the human Major Histocompatibility Complex (MHC) and postulate the existence of a linkage disequilibrium between the LA and/or FOUR alleles and the ICML alleles.…”

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confidence: 63%

Cell Mediated Lympholysis in Man. Varying Strength of the HL‐A (LA and FOUR) Antigens as Sensitizing or Target Determinants

1975

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The gene products of the LA and FOUR loci of the human Major Histocompatibility Complex (MHC) are generally considered to be a major target in the Indirect Cell Mediated Lympholysis (ICML) test. Within most experiments, a positive correlation exists between the number of HL-A antigens challenged and lympholysis. When different experiments are collated this correlation is less obvious. This discrepancy might be caused by differences between the individual HL-A antigens involved in the afferent phase (MLC) a n d o r the efferent phase (CML) .In 28 experiments involving 97 unrelated individuals we have compared statistically 12 different antigens governed by the LA and FOUR loci.When only one of these antigens is challenged in ICML, target lymphocytes are lysed to different degrees allowing a significant classification of the antigens into different groups, which do not coincide with the classification in the LA and FOUR series antigens.I t is concluded that the antigens of the HL-A system are not of equal importance when challenged separately in ICML. The existence of a separate CML locus and a corresponding linkage disequilibrium to the SD loci of the MHC region is suggested.

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confidence: 63%

Cell Mediated Lympholysis in Man. Varying Strength of the HL‐A (LA and FOUR) Antigens as Sensitizing or Target Determinants

1975

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“…In this context, it must be stressed, that the CTLs investigated were raised between donors not fully matched at the HLA-C and HLA-D/DR loci. Determinants from these loci have been shown to serve as target deterrninants for CTLs (Kristensen et al 1975, Grunnet et al 1976, Feighery & Statsny 1979, Albrechtsen et al 1979, Johnsen 1980) although HLA-C determinants were found to be relatively weak targets for destruction and the influence of HLA-D/DR determinants has until now only described on non-PHAlymhoblast targets (monocytes, EBV-transformed B-cell lines and PWM transformed B-cells), even if some PHA-blasts expressed HLA-D/DR. Consequently it is possible that the immuno-dominant traits postulated here are epitopes on the HLA-C and/or HLA-D/DR molecules.…”

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confidence: 99%

Histocompatibility typing by cytotoxic lymphocytes. The HLA‐A2–28, B5‐w35 serologically cross‐reactive groups reviewed by cytotoxic lymphocytes

et al. 1981

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Using a standardized indirect cell-mediated lyrnpholysis (CML) technique, cytotoxic lymphocytes (CTLs) were raised between unrelated, fully HLA-A, B (and C) typed individuals, differing only for one identified HLA-A, B antigenic determinant. Ten CTLs involved HLA-A2+ stimulators and HLA-A2-, A28-, A9-responders. Five CTLs involved HLA-Bw35+ stimulators and HLA-B5-, Bw35-, B15-, B17-, BI8-, Bw21-responders. These CTLs were tested for cell-mediated cytotoxicity against two different panels (20 and 9 cells respectively) of HLA-A28+ and HLA-B5+ PHA-lymphoblasts. The same panel cells were used as cold competitors for cytotoxicity against the specific 51Cr labelled targets.The following observations were made: (1) most panel cells are neither lysed nor able to block; (2) significant lysis is, however, seen in the panels positive for serologically cross-reactive antigens, although lysis is generally lower than comparable lysis by anti-A28 or anti-B5 CTLs; (3) all target cells lysed in the A28 panel are able to inhibit specific lysis while 2 cells in the B5 panel are lysed but do not inhibit (Cytotoxicity-Positive-Inhibition-Negative = CYPIN); (4) a group of panel cells cannot be lysed but are able to inhibit (Cytotoxicity-Negative-lnhibition-Positive = CYNIP).These observations indicate that cross-reactive groups identified by serology may also be identified by celiology using direct cytotoxicity and/or cold target inhibition. The cross-reactivity defined by CTLs, as in serology, is inconstant and often incomplete. Whether the immunogenetic background of cross-reactivity as defined by antibody or CTL is identical is unknown but probable.The occurrence of CYNIP underlines that direct cytotoxicity and cold target inhibition are not directly comparable and indicates that different epitopes may be involved, although the discrepancy may be brought about by the experimental conditions used.The CYPIN phenomenon indicates the existence of immunodominant epitopes although non-T cell-mediated lysis cannot be excluded.

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Differential behavior of cytotoxic effector cells against HLA antigens in strong genetic linkage disequilibrium

et al. 1981

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Five sets of cytotoxic effector cells were generated, using haplo-identical, first degree relatives in five different families, against the HLA-A3; B7 serological determinants combined with different DR antigens. When tested against a panel of cells bearing combinations of the HLA-A, -B and -DR antigens it was shown that the HLA-B7 antigen was as strong a CML target determinant alone as it was in the presence of HLA-A3. The strength of the HLA-A3 antigen as target determinant varied. With effector cells primed to the HLA-A3; B7; DR2 haplotype, the A3 antigen alone behaved as a weak target determinant. When the same target cells were tested with the effector cells generated against HLA-A3; B7 without DR2, the A3 antigen behaved as a strong target determinant. A number of target cells lacking the serologically detectable HLA determinants present on the sensitizing HLA haplotype were identified as being killed by specific effector cells. These data suggest either a number of new CML target determinants controlled by different loci or the presence of a single, new locus with multiple alleles controlling CML targets.

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Cell Mediated Lympholysis in Man. Patterns of Killing Power in Relation to the HL‐A System

Cited by 14 publications

References 7 publications

Cell Mediated Lympholysis in Man. Varying Strength of the HL‐A (LA and FOUR) Antigens as Sensitizing or Target Determinants

Cell Mediated Lympholysis in Man. Varying Strength of the HL‐A (LA and FOUR) Antigens as Sensitizing or Target Determinants

Histocompatibility typing by cytotoxic lymphocytes. The HLA‐A2–28, B5‐w35 serologically cross‐reactive groups reviewed by cytotoxic lymphocytes

Differential behavior of cytotoxic effector cells against HLA antigens in strong genetic linkage disequilibrium

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