The Major Histocompatibility Complex — Genetics and Biology

Bach, Fritz H.; Rood, Jon J. van

doi:10.1056/nejm197610212951705

Cited by 76 publications

(2 citation statements)

References 53 publications

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“…The role of HLA determinants in recognition and/or presentation of conventional antigens may help elucidate the pathogenesis of a variety of diseases. The association of a number of human diseases with certain HLA alleles, probably a reflection of linkage disequilibrium, has become apparent in recent years (1,2). Moreover, juvenile diabetes mellitus (23,24) and ragweed hayfever (25), which are not associated with particular HLA alleles but segregate with the MHC in family studies, may be caused in part by expression of Ir genes encoded in the D region.…”

Section: Discussionmentioning

confidence: 99%

Human immune responses to hapten-conjugated cells. I. Primary and secondary proliferative responses in vitro.

Seldin¹,

Rich²

1978

The Journal of Experimental Medicine

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An in vitro model was developed to study both primary and secondary proliferative responses of human lymphocytes to hapten-conjugated peripheral blood mononuclear cells. Coculture of human lymphocytes with autologous trinitrophenyl (TNP)-conjugated stimulator cells resulted in primary proliferative responses. Subjects segregated into high and low primary responders with mean stimulation indices of 11 and 2.1, respectively. Restimulation of primed cells from high responder subjects 3 wk after initial sensitization generated secondary proliferative responses. To investigate the antigenic requirements for secondary stimulation, autologous TNP-conjugate primed responders were restimulated with both autologous and allogeneic TNP-conjugated stimulators. In all experiments restimulation with autologous conjugated cells yielded substantially greater proliferative responses than with allogeneic conjugates. Experiments were then performed to ascertain whether HLA determinant homology between primed responder and stimulator cells influenced the level of secondary responsiveness. Homology for HLA-A and B locus serologic determinants was not associated with enhanced responsiveness. In contrast, D region determinant homology, detected by B-cell antigen typing, showed a highly significant positive correlation with the magnitude of secondary responses. The data thus strongly suggest that for secondary proliferative responses to TNP, human T cells recognize hapten in association with HLA-D region determinants.

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Section: Discussionmentioning

confidence: 99%

Human immune responses to hapten-conjugated cells. I. Primary and secondary proliferative responses in vitro.

Seldin¹,

Rich²

1978

The Journal of Experimental Medicine

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“…These associations can be very strong -as in ankylosing spondylitis-and serve in diagnosis. For other diseases, such as multiple sclerosis and juvenile diabetes mellitus (Cudworth and Woodrow, 1975;Rubinstein et al, 1977), the demonstration of this association has opened new leads in the study of pathogenesis and etiology (Bach and van Rood, 1976;Neel, 1977). For many of these diseases the association with a given HLA antigen could be explained by linkage disequilibrium between the genes determining the antigen with which the association has been found, and the immuneresponse (Ir) genes.…”

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confidence: 99%

HLA and Complement Typing in Olivo-ponto-cerebellar Atrophy

Wastiaux

Lamoureux

Bouchard

et al. 1978

Can. j. neurol. sci.

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SUMMARY:HLA antigen typing was carried out in a family with an autosomal dominant form of spinocerebellar degeneration [possibly olivoponto cerebellar atrophy (O.P.C.A.) — Type 1] . Eleven ataxic patients, three possibly ataxic subjects, two unrelated spouses and 13 clinically normal at risk siblings were typed for ABO and Rh blood groups, HLA-A and HLA-B antigens, C4 component of the complement and a number of other serum proteins (Clq, (β -1A, (β-1C, C5, (β -lipoproteins). No solid evidence for linkage between the ataxia gene and the HLA or C4 loci could be demonstrated in this family. Certain serum proteins, and particularly β -lipoproteins were found to be significantly reduced in some sub-groups of subjects.

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Change in mixed lymphocyte culture reactivity following allosensitization between DLA‐identical dog sibs

Gluckman

1980

Eur J Immunol

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The mixed lymphocyte culture (MLC) is known to react to major histocompatibility complex disparities but is insensitive to minor histocompatibility antigens. To determine which modifications could amplify reactivity to these antigens, we have studied the effects of presensitization on normally nonresponsive MLC in dogs. Lymphocytes, primed in vitro to and restimulated with cells of a DLA-identical sib, did not react to these specific cells, in contrast to normal proliferation to other stimulators. However, lymphocytes obtained after in vivo sensitization against a DLA-identical donor showed increased reactivity to the donor in approximately half of the recipients. In comparison to primary MLC responses between DLA-mismatched individuals, the [3H] thymidine uptake was less important in this reaction, and peak incorporation was usually not accelerated. This response appeared to be specific in that responsiveness to third-party cells was not increased, and, alternatively, immunization against a DLA haplo-identical donor did not modify reactivity to DLA-identical cells. This increased reactivity after alloimmunization may reflect differences in minor histocompatibility antigens although the skin graft survival time was not significantly shorter in MLC responders than in nonresponder recipients. It seems that in vivo priming is required to expand the number of cells specific for these antigens and to enable detection of proliferation in MLC.

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The Major Histocompatibility Complex — Genetics and Biology

Cited by 76 publications

References 53 publications

Human immune responses to hapten-conjugated cells. I. Primary and secondary proliferative responses in vitro.

Human immune responses to hapten-conjugated cells. I. Primary and secondary proliferative responses in vitro.

HLA and Complement Typing in Olivo-ponto-cerebellar Atrophy

Change in mixed lymphocyte culture reactivity following allosensitization between DLA‐identical dog sibs

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