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Biomedical subjects

S Shaw

Publications and source records attributed to S Shaw.

At least 415 records · Page 23Linked to original sources
PubMed1982

Serologic identification of the human secondary B cell antigens. Correlations between function, genetics, and structure.

The secondary B cell (SB) antigens are polymorphic HLA-linked antigens on human B cells and macrophages that are identified by primed T cell responses but are genetically distinct from the HLA-DR, MB, and MT antigens. Serologic identification of the SB molecule, using the monoclonal antibody ILR1, now makes it possible to correlate the function of these determinants in human T cell recognition with an Ia-like molecular structure and a genetic locus that marks a new HLA subregion. Three lines of evidence indicate that the ILR1 molecule identifies an epitope on some alleles of the SB gene: (a) the polymorphism of ILR1 -reactivity in the population correlates with SB2 SB3; (b) T cell proliferative response to SB2 and SB3 are specifically inhibited by ILR1; and (c) ILR1 reactivity is exactly concordant with the expression of SB2 in a panel of HLA-deletion mutant lymphoblastoid cell line. Together with previous studies, these results indicate that the SB antigens are on Ia-like molecules. Furthermore, the serologic studies of HLA-deletion mutant cell lines demonstrate that there are two HLA regions centromeric to HLA-B controlling expression of Ia-like molecules: a region toward HLA-B that controls expression of HLA-DR, and a region toward GLO that controls expression of SB.

Antibodies, Monoclonal↗
PubMed1982

Recognition of a polymorphic monocyte antigen in HLA.

The serological recognition of 'new' gene products of the HLA system can be accomplished by selecting sera with strong leucocyte antibodies and testing these against a panel of cells obtained from donors which are compatible for the known HLA antigens with the antibody producer. This approach, which we termed the HLA-CAP approach (compatible with antibody producer), was essential in the recognition of what is now called the HLA-DR locus and of non HLA-linked T-cell subgroups. Using the same technique, we have defined here several sera recognizing a structure on monocytes similar to one of the alleles of the HLA-linked PL3 or secondary B-cell (SB) system, so far only recognized by cellular techniques.

Adult↗
PubMed1982

Alloactivated long-term cultured human T lymphocytes express both HLA-DR and SB antigens but lack lymphocyte stimulation capacity.

Cell populations obtained from mixed leukocyte cultures of 6- or 10-day duration were found specifically to restimulate primed lymphocytes detecting HLA-linked SB as well as HLA-D-associated antigens. After expansion in vitro (9-75 days) with medium containing interleukin 2, the cultured cells expressed the T lymphocyte markers detected in indirect immunofluorescence by monoclonal antibodies Lyt-3, OKT3, OKT4, OKT8, and had high levels of HLA-DR antigens. In addition, they were shown in cell-mediated lymphocytotoxicity specifically to express SB antigens of the donor B cell type. Despite their positivity for DR and SB antigens, such cultured T cells failed to restimulate either SB- or D-specific secondary lymphocyte proliferation. Homogeneous cloned populations of cultured T cells also lacked lymphocyte stimulation capacity. In contrast, B cell lines, which also expressed DR and SB antigens, were potent stimulators of both SB- or D-directed proliferation. These data show that the activated T lymphocytes which express both HLA-DR and SB antigens are by themselves unable to stimulate lymphocyte proliferation.

Cells, Cultured↗
PubMed1982

Population studies of HLA-linked SB antigens and their relative importance in primary MLC typing. Analysis of HLA-D homozygous typing cells and normal heterozygous populations.

SB phenotyping was undertaken on 96 HLA-D homozygous typing cells (HTCs) and 129 normal unselected heterozygous donors in the German population, using Interleukin-2-propagated primed lymphocyte typing (PLT) reagents. The results showed that the SB antigens in the normal population behave as a system of alleles at a single locus in Hardy-Weinberg equilibrium (p approximately equal to 0.20). Estimated gene frequencies in the German population appeared to be significantly different (p less than 0.002) from the North American Caucasian population: the principal differences were increased frequencies of the specificities SB1 and SB4, and decreased frequencies of blanks. Of HLA heterozygous donors 41% typed for two distinct SB specificities; 57% typed for one; and 2% were blank. In the HTC group, 20% typed for two specificities; 68% typed for one; and 12% were blank. Thus, a significant proportion of HLA-D homozygous test cells were, nonetheless, heterozygous for HLA-linked SB antigens. Performance of checkerboard mixed leukocyte cultures (MLCs) between 16 SB typed HLA-Dw3 HTCs, however, did not indicate that the observed mutual or one-way responses were influenced in any simple way by SB antigens; neither heterozygosity nor assumed homozygosity for SB antigens appeared to influence the frequency of MLC typing responses of HLA-Dw3-positive donors on these HTCs. These results add further confirmation of the genetic and functional independence of the SB gene product(s) and the HLA-D/DR gene product(s).

Genes, MHC Class II↗
PubMed1982

HLA-SB in the south of France. Correlation between locally derived and reference typing reagents.

The HLA-D region of the Major Histocompatibility Complex has been subdivided since 1978 (Mawas et al. 1978) into two subregions separable by recombination: a telomeric subregion (closer to HLA-B), coding for the classical HLA-DR or Dw specificities (Mawas et al. 1980) as well as for the more recent MT series (Park et al. 1980); and a centromeric subregion (closer to GLO), coding for a new series of alleles provisionally named SB (for secondary B cell antigens) (Shaw et al. 1980, 1981a). Reagents allowing the identification of six independent alleles have been characterized in two laboratories (Charmot et al. 1980 and Shaw et al. 1980, 1981b) using the technology of primed lymphocytes typing (Sheehy et al. 1975; Mawas et al. 1975). The existence of this new locus is supported by the following arguments: population studies by Shaw demonstrating five traits distinct from DR behaving as alleles (Shaw et al. 1981b), analysis of two informative SB/DR recombinant families (Mawas et al. 1978; Mawas et al. 1980; Shaw et al. 1981a), and, finally, studies of mutants showing independent loss of DR expression without loss of SB expression (Kavathas et al. 1981). The present report summarizes the HLA-SB typing of 109 unrelated individuals from the South of France and segregation studies in 14 unrelated families; a first attempt to correlate local "SB" reagents with the NIH reference standards is presented.

Female↗
PubMed1982

Killing of measles virus-infected cells by human cytotoxic T cells.

Lymphocytes from normal individuals were tested for the capacity to generate measles virus-specific cytotoxic T-cell responses after in vitro stimulation with measles virus. Approximately 12% (5 of 40) of the normal adults tested produced significant cytotoxic responses. The cytotoxic response was measles virus specific both at the level of stimulation and at the effector level. Studies of the specificity of cytotoxic effectors from five normal donors by direct lysis or cold target inhibition or both indicated that most, if not all, of the virus-specific activity was self-specific. A detailed analysis of one donor (W6) indicated that measles-specific cytotoxicity was largely HLA-A and -B restricted; unexplained cross-reactive lysis was observed with some targets, but this lysis appeared to be HLA related, since all of the targets expressed HLA-B12. An analysis of the cellular requirements for the production of measles-immune cytotoxic T lymphocytes demonstrated that T cells and macrophages (depleted of natural killer and K cells) were sufficient for the generation of killer cells. Most of the cytotoxic effector activity was mediated by OKT3+ OKT4- OKT8+ cells.

Adolescent↗
PubMed1982

Analysis of the HLA-linked SB gene system with cloned and uncloned alloreactive T-cell lines.

Further enhancement of cellular typing for antigens of the new HLA-linked "SB" gene was undertaken by T-cell expansion and cloning. The PLT reagents which define these antigens could be expanded over 100-fold with interleukin 2 (IL-2), without loss of specificity. Cloning efficiencies in limiting dilution of over 50 percent could be achieved, although only 5 percent of these could be expanded extensively. Detailed analysis was performed with clones from a highly restricted PLT reagent raised between an HLA recombinant donor and his sibling whose only known HLA difference was SB4. The antigens recognized by the 11 independent clones analyzed appeared to segregate in this family with HLA. Although the two SB4-positive haplotypes in the family were essentially indistinguishable by the clones, they detected heterogeneity among unrelated donors matched for SB4 (as defined by bulk PLT reagents). Such heterogeneity did not appear to be due to differences between clones in the kinetics of their responses, but could be explainable by complexity of the SB molecule or by new HLA antigens.

B-Lymphocytes↗
PubMed1982

Two subgroups of HLA Bw44 defined by cell-mediated lympholysis that differ in Bw44 expression on platelets and in patterns of genetic linkage disequilibrium.

Possible immunogenic heterogeneity of the HLA-Bw44 antigen was investigated using cytotoxic T lymphocytes (CTL) generated between donors identical for HLA-A2,3,-B7,w44. Highly discriminatory CTL combinations were identified that defined two subgroups of Bw44, designated 44.1 and 44.2. Out of 47 Bw44-positive donors tested in a population study, 30 were lysed by the CTL defining 44.1, and 19 were lysed by the CTL defining 44.2. All Bw44 cells could be typed as either 44.1 or 44.2, except two Bw44-positive cells that were phenotypically homozygous for the serologically defined Bw44 antigen and were lysed by both CTL. No Bw44-negative donors (zero out of 37) expressed either 44.1 or 44.2, although cold target blocking was required to eliminate a contaminating reactivity of one CTL population on Bw35 and some Bw45 cells. CTL were also raised between responder/stimulator combinations mismatched for Bw44. These CTL lysed all Bw44-positive target cells, indicating a CML antigen shared by all Bw44 cells. But clear discrimination of the 44.1 and 44.2 subgroups was obtained when appropriate cold target blocking cells were added. All donors with 44.2 expressed high levels of serologically detectable Bw44 on their platelets, and all with 44.1 expressed low levels (p less than 0.005). Furthermore, population studies indicate that 44.1 is in positive linkage disequilibrium with HLA-A2 and possibly DR4, whereas 44.2 is in positive linkage disequilibrium with HLA-DR7 and possibly HLA-A23, -A26, and -A29. These data suggest the existence of two genetically and functionally different subgroups of Bw44 antigens.

Blood Platelets↗
PubMed1981

Cytotoxic T cell interactions with antigen. Potential relevance for drug-related lupus.

Understanding of cytotoxic T cell recognition may be relevant to the study of drug-related lupus because either cell-mediated cytotoxicity (CMC) contributes to triggering the disease or CMC provides an informative model to study T cell recognition of foreign antigen. As a model, CMC demonstrates the following: 1) Antigen presentation can occur by membrane insertion of the antigen, covalent modification of the cell surface, or cell surface adsorption of the antigen; these may be modes of presentation by which drug-related antigens induce adverse responses. 2) HLA antigens regulate a wide variety of immune responses; this may be crucial in drug-related lupus since HLA antigens may regulate autoimmune responses, may affect an individual's susceptibility to lupus, and may increase the risk for other specific adverse drug reactions.

Antigens↗
PubMed1981

Population studies of the HLA-linked SB antigens.

Using allogeneic T-cell recognition we have previously defined five new histocompatibility antigens designated "SB" antigens. To standardize typing for these antigens, cryopreserved, primed lymphocytes are now used as standard reagents and a technique of cluster analysis has been modified to score typing results objectively. Two primed lymphocyte reagents are used to define each SB antigen; although derived from independent responder-stimulator combinations, the concordance between the reagents is good (r is greater than 0.86). The SB-antigen distribution in a population of 215 normal donors in consistent with Hardy-Weinberg equilibrium of alleles of a single locus. Estimated gene frequencies ranged between 3 percent (SB5) and 36 percent (SB4) with 31 percent blanks. Analysis of association between the SB antigens and A, B, DR antigens in 200 normal donors revealed that associations were generally weak with a few exceptions, in particular, the A1, B8, DR3, SB1 "haplotype" and also the B7, DR2, SB5 "haplotype".

Gene Frequency↗
PubMed1981

Therapeutic renal artery occlusion with a detachable balloon.

The use of a new detachable balloon for renal artery occlusion is described. Successful treatment of renal lesions in 5 patients, including 2 tumors, 2 arteriovenous fistulas and 1 case of malignant hypertension with renal failure, is reported.

Adult↗