Frequency estimations of cytotoxic precursors to trinitrophenyl-modified alloantigens and determination of the degree of cross-reactivity between allodeterminants and trinitrophenyl-modified self determinants

A clonal assay for precursors of cytotoxic T lymphocytes (CLP) was used to determine the frequency of CLP specific for trinitrophenyl (TNP)-modified alloantigens. It was found that the frequency of CLP to TNP-modified alloantigens is about 13% of the CLP frequency to unmodified alloantigens. This assay system was also used to estimate the degree of cross-reactivity between allodeterminants and TNP-modified self determinants. About 16% of the cytotoxic clones activated by alloantigens can also kill TNP-modified syngeneic targets. The relevance of these findings to the adaptive differentiation model is discussed.     

Confirmation of a susceptibility locus on chromosome 13 in Australian breast cancer families

Two major genes determining predisposition to breast cancer, termed BRCA1 and BRCA2, have been mapped to the long arms of chromosomes 17 and 13, respectively. Each locus is believed to account for approximately 40% of cases of familial breast cancer. We used linkage and haplotype analysis with simple tandem repeat polymorphisms at chromosomal bands 17q21 and 13q12 to determine the contribution of the BRCA1 and BRCA2 genes to predisposition to breast cancer in four Australian breast cancer kindreds, one of which had two male cousins with breast cancer. Surprisingly all families segregated a haplotype of markers on 13q and showed positive lod scores supporting linkage to BRCA2. In addition, haplotype analysis identified an informative recombination between D13S260 and D13S171 in one affected individual, which refines the localisation of BRCA2 to between D13S260 and D13S267; a distance of 2–3 cM. Tumours of the stomach and cervix, as well as melanoma and leukaemia/lymphoma also occur in these pedigrees but the numbers are too low to determine whether they may be significantly associated with BRCA2 carrier status. Our results confirm the existence of BRCA2 on the long arm of chromosome 13 and support previous findings that this locus is likely to confer risk in families with affected males. Furthermore, our observations suggest that the BRCA2 gene may also contribute to the development of other neoplasms. Received: 26 September 1995 / Revised: 15 January 1996