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We have identified a novel activation related B-cell gene (bca) through differential hybridization screening of a murine B cell cDNA library. The deduced amino acid sequence predicted a protein of 482 amino acids with strong sequence similarity to the SH2 and SH3 domains present within the non-catalytic regions of several protein tyrosine kinases. Northern analysis of RNA from several murine B-cell lines revealed a transcript of 1.8 kb, which was not detected in T-cell and non-lymphoid cell lines. bca was transcribed at low levels in resting spleen cells from a variety of normal mouse strains and was strongly expressed in kidney RNA. bca expression was markedly increased in RNA prepared from mitogen activated B cells, and in freshly isolated spleen and lymph node cells of MRL/lpr and NZB autoimmune strains. The unique sequence of bca, which bears no obvious similarity to any specific class of proteins containing SH2 and SH3 domains, suggests that this gene encodes a novel protein potentially involved in B-cell signal transduction.

A physical chemical model of T cell stimulation by class I-peptide complexes was developed and used to analyse in vitro studies of γ-interferon release as a function of the number of peptide and MHC molecules. The analysis provided reasonable estimates of well identified parameters, including equilibrium constants and the minimum number of T cell receptor-class I-peptide ternary complexes on a presenting cell required to activate T cells. The latter number was estimated as 3–5 per T cell. This is in distinct contrast to estimates in the literature of the number of peptide-MHC complexes required for activity, which is necessarily larger. The analysis also predicted that activity is potentiated by interaction between class I molecules, even if one member of the pair is not bound by antigen. The analytical approach used in this paper may be applicable to other activation systems.

Natural killer (NK) cell function is regulated by NK receptors that bind either classical MHC class I (MHC-I) molecules or their structural relatives (MICA, RAE-1 and H-60). Two distinct families of NK receptors have been identified: the C-type lectin-like family (Ly49, NKG2D and CD94/NKG2) and the immunoglobulin-like family (KIRs and LIRs). Here, we describe the crystal structure of the C-type lectin-like NK receptor (Ly49A), bound to its MHC-I ligand (H-2D(d)). We also discuss results from recent mutagenesis studies of the Ly49A/H-2D(d) interaction in the context of the complex structure.