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B7-1 and B7-2 are members of the immunoglobulin superfamily (IgSF) and important regulators of T cell-mediated immune responses. Despite sharing only limited sequence identity, B7-1 and B7-2 bind common receptors, CD28 and CTLA-4, on T cells and have similar functional properties. We have found that the extracellular V(ariab1e)-like domains of B7-I and B7-2 share significant sequence similarities with 3 major histocompatibility complex (MHC)-encoded members of the IgSF: butyrophilin, myelin/oligodendrocyte glycoprotein, and the chicken MHC molecule, B-G. This raises the question whether there is an evolutionary link between the MHC, which encodes molecules regulating the antigen specificity of T lymphocyte responses, and B7 molecules, which co-stimulate these responses in antigen-nonspecific fashion.Keywords: B7; immunoglobulin superfamily; sequence similarity; structural similarity; T cell-mediated immunity Binding of CD28 and/or CTLA-4 receptors on T cells to B7 (CD80)-related molecules on antigen-presenting cells triggers a T cell co-stimulatory pathway required for optimal immune responses (Linsley & Ledbetter, 1993). Two B7-related molecules have been cloned from man and mouse: B7-I (Freeman et al., 1989, 1991) and B7-2 (Freeman et al., 1993a, 1993b) or B7-0 (Azuma et al., 1993. These molecules are members of the immunoglobulin superfamily (IgSF), comprising a V(ariab1e)-like and a C(onstant)-like domain in their extracellular regions. B7-1 and B7-2 share functional properties of binding to CTLA-4 and of co-stimulating T cell responses (see Linsley & Ledbetter, 1993, for review), despite having only -25% amino acid sequence identity in their extracellular domains.As part of ongoing efforts to elucidate the molecular basis of interactions between B7-related molecules and their receptors on T cells, we have analyzed the sequences of B7-related molecules relative to other members of the IgSF. We show that much of the sequence identity in the IgSF V-like domains of B7-1 and B7-2 beyond established IgSF consensus residues is shared with 3 other members of the IgSF, which are related: butyrophilin IgSF V-like domains were analyzed using the GCG package (Genetics Computer Corporation, Inc., Madison, Wisconsin, 1993). Two sequence comparison tables (Dayhoff et al., 1979;Risler et al., 1988) were used and gave similar results. Alignments were performed using PILEUP; position-specific sequence profiles were calculated using PROFILEMAKE and used to search the Swiss Protein Database with PROFILESEARCH. A profile calculated from the V-like domains of B7-1 and B7-2 showed higher sequence similarity with BT than with all other sequences in the Swiss Protein Database ( Z = 6.9; Z scores >5 are considered statistically significant). Another profile was calculated from B7-l, B7-2, and the V-like domain of BT, and again used for database searching. This profile revealed higher similarity with MOG ( Z = 12.4) than with all other sequences in the Swiss Protein Database; incorporation of MOG into the profile then ga...

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Purpose: This is a retrospective analysis of the isolation rates of nontuberculous mycobacteria (NTM) from various clinical specimens and their antimicrobial susceptibility patterns. Methods: All NTM isolated between 1999 and 2004 at Christian Medical College, Vellore, South India, were identified with various biochemical tests. Antimicrobial susceptibility test for all NTM was performed by standard methods. Results: A total of 32,084 specimens were received for culture, of which 4473 (13.9%) grew acid fast bacilli (AFB). Four thousand three hundred (96.1%) of the AFB were M. tuberculosis while 173 (3.9%) were NTM. Of the 173 NTM, 115 (66.5%) were identified to the species level. Pus, biopsy specimens and sputum specimens yielded most of the NTM of which M. chelonae (46%) and M. fortuitum (41%) accounted for majority of them. M. chelonae and M. fortuitum, showed highest susceptibility to amikacin (99.2%). NTM were repeatedly isolated from seven sputum specimens, 15 biopsy and pus specimens, two CSF and two blood cultures. Six were isolated from patients with AIDS and five from post transplant patients. Conclusions: The isolation of NTM from various clinical specimens is reported in this study to highlight the associated diseases and therapeutic options in these infections. 1 NTM comprising of over 95 species are naturally seen as saprophytes 2 but are known to cause four different categories of infections in humans such as, i) pulmonary infections resembling tuberculosis, ii) extra pulmonary infections affecting lymph nodes, skin and soft tissue, iii) multifocal disseminated infections and iv) infections in immunocompromised individuals such as AIDS and transplant patients.3 The growing population of HIV infected individuals and other immunosuppessed / immunocompromised patients coupled with better diagnostic techniques has led to an increase in the number of NTM being reported in human infections in recent years. 4 NTM produce infections more commonly in the presence of predisposing factors / underlying diseases; they are also notably resistant to commonly used antitubercular drugs. These factors augment morbidity and limit therapeutic options in such infections. NTM have been reported world wide with varying frequencies, 5-8 while in India isolation rates are between 0.7% and 34%. 9 We have reviewed the isolation rates of NTM from various clinical specimens over a period of six years at the department of Clinical Microbiology, Christian Medical College, Vellore -South India. Through this study we wish to emphasize the need to look for NTM in various clinical specimens. Materials and MethodsThis study includes the isolation of NTM from all clinical specimens from suspected pulmonary and extra pulmonary tuberculosis received between 1999 and 2004. Early morning well coughed out sputum specimens, broncho alveolar lavage, bronchial wash and endotracheal aspirate specimens were received from patients with clinical and radiological findings suggestive of pulmonary tuberculosis. From children and patients fro...

Somatic cell hybridizations were performed between an HLA-DR negative variant of a human B lymphoid cell line (B-LCL) and normal unrelated B-LCLs. The HLA-DR codes for polymorphic determinants on a heterodimeric cell surface lymphocyte differentiation glycoprotein. A variant subline which was selected in a single step from a diploid heterozygous DR-1 DR-3 B-LCL had lost expression of both DR-1 and DR-3 and the heretodimer; it has been described earlier. In a fusion with a DR-2 B-LCL, the hybrids expressed DR-2 and reexpressed the DR-1 and DR-3 alleles. Similar results were seen in a fusion with a different normal B-LCL. Hybrid clones from both fusions were tested with a large number of alloantisera and essentially all informative sera showed reexpression. The results show that (1) the variant did not arise by mutations in the structural genes for DR-1 and DR-3; (2) the normal cells are supplying a missing gene product needed for expression of DR; (3) this gene product is capable of acting in trans. Chromosome counts showed that the apparent recessiveness of the variant in the hybrids was not due to chromosomal segregation.