HLA and malignancy : proceedings of a symposium presented by Roswell Park Memorial Institute, Buffalo, New York, August 19-20, 1976 / editor in chief: Gerald P. Murphy; associate editors: Elias Cohen, John E. Fitzpatrick, David Pressman.

Date:
1977
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Licence: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)

Credit: HLA and malignancy : proceedings of a symposium presented by Roswell Park Memorial Institute, Buffalo, New York, August 19-20, 1976 / editor in chief: Gerald P. Murphy; associate editors: Elias Cohen, John E. Fitzpatrick, David Pressman. Source: Wellcome Collection.

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    Genetic and Immunologic Considerations / 3 but reproducible increase in the freqneucy of A2 is found in acute lymphocytic leukemia (8), and the 3-7 and 3-14 haplotype is frequently found in hemochro¬ matosis, suggesting a frequent association with an A locus allele (9). Many HLA- associated diseases tend to be most frequent in individuals with a particular HLA specificity at the population level. Other diseases, such as ragweed hay fever, may segregate with one of the haplotypes in a family, and do not appear to be asso¬ ciated with any particular allele in a population (10). In the mouse, develop¬ mental abnormalities may be caused by alleles of loci linked to H-2 (cleft palate, brachyury), and there are important interactions between some viruses and H-2 and with chemical haptens. At least two powerful series of immune response genes (in the lA and 1С region) are also closely linked to H-2, as are genes con¬ trolling complement components. Susceptibility to Gross, Friend, Rauscher, Maloney, Rous, Bittner, and Tennant virus-related neoplasms are all Н-2-associated. Evidence for similar associations with HLA in man are being sought for or are accumulating. Interestingly, choice of mate appears to be associated with some Н-2-related characteristic, possibly scent (11). While some individuals have been seen to sport badges questioning Are you my HLA type? there is as yet no systematic study of this point! These, then, are some of the salient facts about the major histocompatibility complex. We would now like to discuss some of the less well-known attributes of the system with special reference to reactions demonstrated by the anti- globuHn cytotoxicity test (ACT), by lymphocyte-dependent-antibody-mediated reactions (LDA). The antiglobulin cytotoxocity test uses rabbit or goat anti-whole human globulin to develop additional reactions in the conventional microcytotoxicity test (12). The test involves the addition of alloantibody to lymphocytes in microcytotoxicity plates and incubation for 60 min. The cells are then washed by adding buffer to fill the wells with mixing. The plates are centrifuged, the supernatant is removed by ñicking. This wash, pack, flick cycle is repeated three or four times (13). Interestingly, this wash manipulation by itself greatly increases the sensitivity of the test. Many reactions that are negative without washing or with only one wash become strongly positive, while controls and responses to some sera remain negative. Antiglobulin diluted to a predetermined level of maximum lytic effect is added, and followed after 1 min by comple¬ ment. This further increases the sensitivity of the test. Not all antiglobulin sera are effective, and the effectiveness is not related to the precipitin titer of the serum. Further, in unpublished experiments per¬ formed by the authors in collaboration with Dr. Jenny Goudemand of Lille, France, it was shown that precipitation of the antiglobulin with purified IgG or with whole serum did not diminish the potentiating effect of the antiglobulin serum. The potentiating effect does, however, appear to be due to antibody, since it has specificity and is complement-dependent, and the reaction is, in most