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The immune system employs a temporal hierarchy of effector mechanisms to combat infections by intracellular pathogens. The nonspecific response is independent of MHC and can be activated rapidly, while the specific response is slower, more specific, and requires major histocompatibility complex (MHC) molecules. MHC-dependent responses have been characterized extensively in vitro for antigens presented by polymorphic MHC class Ia and class II proteins and recognized by T lymphocytes carrying alpha/beta T-cell receptors (TcR). Growing indirect evidence has implicated monomorphic MHC class Ib proteins and gamma/delta T lymphocytes in defense against bacterial infections, but the biochemical and immunological behavior of class Ib proteins and gamma/delta TcR has not been well characterized, and most hypotheses involving these proteins have relied on data obtained with polymorphic MHC proteins and alpha/beta TcR. An overview of studies describing bacterial infections in vivo suggests that, in many cases, MHC class I-dependent effector cells may not be indispensable for effective immune responses, exerting instead a modulatory effect during the course of infection. Furthermore, many class Ib proteins have probably specialized to present stress antigens and conserved microbial antigens, which may be recognized by gamma/delta T cells through an interaction that is qualitatively very different from alpha/beta TcR binding to class I and class II proteins.

The class I Ag encoded in the Qa/T1a regions of the murine MHC are much less polymorphic, and usually have a more restricted tissue distribution than the classical histocompatibility class I Ag, encoded by genes located in the H-2K, D, and L loci. The isolation of a quasi-ubiquitously expressed, poorly polymorphic class I gene of the T1a region of the H-2d mouse MHC, namely gene 37 (or T18d), has been recently reported. We describe the nucleotide sequence of a closely related gene, T10c gene, the counterpart of the gene 37 in the large duplicated parts of T1a region of the BALB/c (H-2d) MHC. The T10c gene structure and sequence are very similar to those of gene 37, but T10c gene is most likely a pseudogene. In A/J mouse strain, there appears to be a single gene related to 37, which is also found expressed in a variety of tissues. We show that this gene is likely to be a chimeric one derived from T10c for its 3' part, and from a gene closely related to gene 37 for its 5' part, which potentially encodes for an unusual class I molecule composed of the first two domains. Finally, Southern blot analysis of a number of wild mice and related animals suggests that a gene closely related to the present T10c gene may be the ancestor of this subfamily of class I genes characterized by the presence of an unusual second domain.

We have isolated a cDNA clone carrying a 1560 bp long insert which contains the entire coding and 3' untranslated regions of an H-2K(d) mouse histocompatibility antigen. Its sequence and overal features are described. They point to the existence of unique properties of DNA sequences associated with the H-2K(d) antigen.

A cDNA library constructed from liver mRNA of DBA/2 (H-2d) mice has been screened with H-2-specific probes. The nucleotide sequence of one clone (pH-2d-24) indicates that it derives from an H-2 gene with an unexpected exon-intron organization. Nucleotide sequence comparisons suggest that two distinct mRNAs are produced from a single H-2Kd gene by a mechanism involving the use of alternative splicing sites in its 5' region. pH-2d-24 carries an open reading frame encoding a thus-far-undescribed polypeptide product identical to an H-2Kd-molecule, except for the NH2-terminal half of the first domain.

mRNA coding for mouse major transplantation antigens of the d haplotype was partially purified, copied into double-stranded cDNA, and cloned in Escherichia coli. Clones were selected by their ability to hybridize specifically with mRNA coding for H-2K, D, or L antigens. One of these clones, pH-2d-1, carries a 1200-base-pair insert, comprising the noncoding region, including poly(A) at the 3' end and part of the coding region. A partial sequence of the latter region showed extensive homology with the known amino acid sequences of H-2Kb,Kk, and HLA-B7 antigens. From this comparison, it appears that the coding region extends from amino acid 133 in the second domain, through the third domain, to the cytoplasmic COOH-terminal region. A stretch of 24 hydrophobic or uncharged residues, located 31 amino acids from the COOH-terminal end, could represent the segment that spans the membrane. This is followed on the cytoplasmic side of the membrane by a cluster of basic amino acids and a possible phosphorylation site on a threonine residue.

The complete nucleotide sequences of three cDNAs coding for the C-terminal part of mouse histocompatibility (H-2) antigens, and for the 3' non coding regions of these clones have been determined. Comparison of the sequence indicates a large homology throughout the coding and non-coding regions and suggests the existence of a genetic mechanism which homogenizes nucleotide sequences among genes of the H-2 multigene family.

During their ageing, MRL-lpr/lpr mice (H-2k) suffer from progressive lymph node enlargement, associated with the development of several acute autoimmune lesions. The primary effect and location of the lpr mutation is unknown. However, a minority of the lymphoid cells of some MRL-+/+, as well as MRL-lpr/lpr mice, express 'alien' H-2d antigenic specificities. In the course of the investigation of the origin of the latter, we have carried out the genotyping of the MHC of several MRL-+/+ and MRL-lpr/lpr mice using the Southern blotting technique and employing a variety of MHC class I and class II probes, and restriction enzymes known to discriminate between the d and the k haplotypes. None of the results obtained so far suggests the contribution of genuine H-2d genes to the MHC of the MRL-+/+ and MRL-lpr/lpr mouse strains. Alternative hypotheses for the generation of the 'alien' epitopes are discussed.