Serum beta 2-microglobulin binds to a T-cell differentiation antigen and increases its expression

The human T-cell leukaemia and differentiation antigen HTA 1 is defined by the monoclonal antibody NA1/34 (ref. 1) and also recognized by the monoclonal antibody OKT6. Like class I products of the human major histocompatibility complex, it has a glycosylated heavy (alpha) chain of approximately 45-50,000 molecular weight (MW) in non-covalent association with beta 2-microglobulin (beta 2m) (MW 11,900). A particular feature of HTA 1 is the presence in significant amounts of an additional beta 2m-like subunit, called beta t (refs 3, 4). Top facilitate biochemical studies we have prepared a high HTA 1 expressor variant (NH17) of the human thymoma line MOLT-4. The N-terminal amino acid sequence of the beta t purified from this cell line was shown to be indistinguishable from that of bovine beta 2m. Further, beta t was present when the cells were grown in medium containing fetal calf serum (FCS), but absent from cells grown with human serum (HuS). We show here that addition of human and bovine beta 2m to MOLT-4 and NH17 cells grown in serum-free medium produces a significant elevation of HTA 1 antigen expression, providing evidence for a regulatory or stabilizing function for the exchange of extracellular beta 2m with a cell-surface antigen.     

Common sequence variants on 20q11.22 confer melanoma susceptibility

We conducted a genome-wide association pooling study for cutaneous melanoma and performed validation in samples totaling 2,019 cases and 2,105 controls. Using pooling, we identified a new melanoma risk locus on chromosome 20 (rs910873 and rs1885120), with replication in two further samples (combined P < 1 x 10(-15)). The per allele odds ratio was 1.75 (1.53, 2.01), with evidence for stronger association in early-onset cases.     

Genome-wide association study identifies three new melanoma susceptibility loci

We report a genome-wide association study for melanoma that was conducted by the GenoMEL Consortium. Our discovery phase included 2,981 individuals with melanoma and 1,982 study-specific control individuals of European ancestry, as well as an additional 6,426 control subjects from French or British populations, all of whom were genotyped for 317,000 or 610,000 single-nucleotide polymorphisms (SNPs). Our analysis replicated previously known melanoma susceptibility loci. Seven new regions with at least one SNP with P < 10(-5) and further local imputed or genotyped support were selected for replication using two other genome-wide studies (from Australia and Texas, USA). Additional replication came from case-control series from the UK and The Netherlands. Variants at three of the seven loci replicated at P < 10(-3): an SNP in ATM (rs1801516, overall P = 3.4 × 10(-9)), an SNP in MX2 (rs45430, P = 2.9 × 10(-9)) and an SNP adjacent to CASP8 (rs13016963, P = 8.6 × 10(-10)). A fourth locus near CCND1 remains of potential interest, showing suggestive but inconclusive evidence of replication (rs1485993, overall P = 4.6 × 10(-7) under a fixed-effects model and P = 1.2 × 10(-3) under a random-effects model). These newly associated variants showed no association with nevus or pigmentation phenotypes in a large British case-control series.