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C M Graham

Publications and source records attributed to C M Graham.

34 records · Page 2Linked to original sources
PubMed1989

I-Ad restricted T cell recognition of influenza hemagglutinin. Synthetic peptides identify multiple epitopes corresponding to antibody-binding regions of the HA1 subunit.

In a recent study, we reported extensive diversity in the Iak-restricted T cell repertoire for the hemagglutinin molecule (HA) of influenza A viruses (H3 subtype). Synthetic peptides identified six nonoverlapping epitopes on the HA1 subunit, and CD4+ T cell clones, specific for these regions, discriminated between natural variant viruses that had accumulated amino acid substitutions during antigenic drift. Here, we demonstrate similar specificity and diversity for the Iad haplotype and have identified multiple T cell epitopes within the sequences HA1 56-76, 71-91, 81-97, 177-199, 186-205, and 206-227. These also include recognition sites for neutralizing antibodies and correlations can be made between antigenic drift substitutions in H3 subtype viruses and the specificity of individual CD4+ clones for mutant HA. Moreover, these peptides appear not to exhibit structural homology and fail to compete for Ag presentation, indicating heterogeneity in peptide-Ia interaction. To explain the observation that CD4+ T cells, from two major haplotypes, recognize antibody binding regions of the HA molecule, we propose that surface Ig receptors of the Ag-specific B memory cell exert a direct effect on the processing of HA peptides and subsequent selection of the class II-restricted T cell memory repertoire after natural infection.

Amino Acid Sequence↗
PubMed1989

Immune recognition of influenza virus haemagglutinin.

Haemagglutinin glycoproteins are the components of influenza virus membranes against which infectivity-neutralizing antibodies are directed. Sequence analysis of natural and laboratory-selected variant haemagglutinins indicates the regions of the molecule recognized by antibodies and by helper T cells; the identity of these regions and the relations between them are discussed.

Amino Acid Sequence↗
PubMed1989

The immune response of BALB/c mice to influenza hemagglutinin: commonality of the B cell and T cell repertoires and their relevance to antigenic drift.

An extensive analysis of the class II (I-Ad)-restricted T cell repertoire for influenza hemagglutinin (HA) of the H3 subtype, elicited by natural infection, has shown that majority of CD4+ memory T cell clones focus on antibody-binding regions of HA, sites B and E, and are sensitive to the residue substitutions that have occurred in these regions during antigenic drift. The proliferative responses of CD4+ clones to synthetic peptides have identified T cell epitopes within site B, HA1 177-199 and HA1 182-199, and site E. HA1 56-76. The recognition specificity of T cell clones for antibody-selected mutant viruses, with single amino acid substitutions within these recognition sites identified residues 63, 189, 193 and 198 as being important for T cell recognition and thus established that BALB/c, CD4+ T cell clones were sensitive to the same substitutions known to abrogate BALB/c antibody recognition of the native HA. Our findings indicate extensive commonality of the B cell and T cell repertoires for HA, which may be relevant to an understanding of the immune pressures for antigenic drift, and, moreover, suggest that the antigen-specific B memory cell may be instrumental in selection of the peripheral T cell repertoire.

Animals↗
PubMed1989

The structural requirements for class II (I-Ad)-restricted T cell recognition of influenza hemagglutinin: B cell epitopes define T cell epitopes.

A majority of I-Ad-restricted CD4+ clones elicited by influenza X31 (H3N2) virus infection, recognize a synthetic peptide of hemagglutinin (HA) corresponding to an antibody binding region of the HA1 subunit (site B: HA1 177-199). The structural requirements for class II-restricted T cell recognition were investigated by determining the proliferative responses of representative CD4+ clones to truncated HA1 peptides and synthetic peptide analogues. Two distinct T cell epitopes were identified and CD4+ clones, specific for either determinant, were sensitive to the same single amino acid substitutions in synthetic peptides at HA1 193 S----N or HA1 198 A----E, that had featured in antigenic drift and abrogated antibody binding to native HA. Competitive inhibition studies, between stimulatory HA1 peptides and non-stimulatory analogue peptides, for antigen presentation to CD4+ clones established that the 193 S----N and 198 A----E substitutions could affect either interaction with the T cell receptor or class II molecule, according to the specificity of the CD4+ clone examined. The structural requirements for class II-restricted T cell recognition of the linear sequence determinants of HA are, therefore, integrally linked to conformation-dependent antibody recognition of the native molecule.

Amino Acid Sequence↗
PubMed1989

Intrascleral neurilemmoma.

The case of an anteriorly situated, intrascleral, neurilemmoma in an 11-year-old girl is reported. Only two similar cases have been described in the literature, and the diagnosis was made only after detailed histological examination, including electron microscopy and specialised staining techniques, to differentiate a neurilemmoma (schwannoma) from a neurofibroma.

Child↗
PubMed1988

Amblyopia and strabismus in congenital ptosis.

Seventeen per cent of 216 cases of simple congenital ptosis developed amblyopia and 19% had a squint. Of those patients with amblyopia, 14% had amblyopia attributable to stimulus deprivation, 21% had anisometropic amblyopia and 51% had strabismic amblyopia. Early refraction, orthoptic assessment and treatment and, where the pupillary axis is occluded, surgery to prevent stimulus deprivation amblyopia are recommended.

Amblyopia↗
PubMed1988

Prospects for contact lens wear in aphakia.

The success rate and complications for contact lens wear in 366 aphakic patients were evaluated retrospectively over a mean follow-up period of 36 months. Successful use of a daily wear contact lens (DWCL) was related to lens handling ability. In unilateral aphakia it was 86 per cent (161/187) for patients under 70 years old but only 27 per cent (19/70) for those over 70 years (p = less than 0.0001). This age related difference did not occur either for the use of a second lens, following successful use of a lens after the first cataract extraction, for which the overall success rate was 89 per cent (55/62) or for simultaneous bilateral lens fitting, which had a success rate of 81 per cent (38/47). Extended wear soft contact lenses (EWSCL) were fitted to patients unable to use DWCLs but only half were successful (21/40). There was no difference in the incidence of complications between daily wear soft and daily wear hard contact lenses or young (up to 44 years), middle aged (45-69 years) and elderly (over 70 years) patients, for the use of all DWCLs. However the risk of a serious complication was six times greater for patients using EWSCL (55 per cent) compared with those using DWCLs (8.8 per cent). DWCLs are a safe and successful method of aphakia correction for patients under 70 years of age. Once the ability to handle a DWCL has been learned, success is maintained when the second eye is fitted. EWSCLs have a high complication rate and a low success rate in patients unable to use DWCLs; other methods of aphakia correction should be considered first in this group.

Adult↗
PubMed1988

Indomethacin retinopathy: case report and review.

The case of a 33-year-old man with probable indomethacin retinopathy is presented. The relevant literature is reviewed and the differences between our case and those previously reported are noted. Our patient appears to have suffered severe and irreversible ocular damage due to the very high dose of indomethacin ingested over a prolonged period.

Adult↗
PubMed1987

A single amino acid substitution in influenza hemagglutinin abrogates recognition by monoclonal antibody and a spectrum of subtype-specific L3T4+ T cell clones.

A fine specificity analysis of influenza hemagglutinin-specific IAk-restricted T cell clones using natural virus variants of the H3N2 subtype, monoclonal antibody-selected variants and a synthetic peptide corresponding to a variable region of the HA1 polypeptide has provided insight on the structural basis for T cell recognition. A glycine to arginine substitution at HA1 135 abrogates recognition by a panel of T cell clones which, according to their reactivity for natural virus variants, have different antigenic specificities: three clones recognize a synthetic peptide (HA1 residues 118-138) but fail to recognize the monoclonal antibody-selected mutant (Gly135/Arg). There is no correlation, however, between differences in T cell specificity for the natural virus variants and HA1 amino acid sequences in this region. Two further clones have a reduced proliferative response to mutant recognize a completely different spectrum of natural variants, and only one of these clones recognizes the synthetic peptide. We speculate that influenza hemagglutinin employs a common strategy during antigenic drift to evade antibody recognition and effective processing/presentation to subtype-specific T cell clones.

Amino Acid Sequence↗
PubMed1986

Autoimmunity to Thy-1.

Conditions are described for the induction of autoimmunity to Thy-1 and a large panel of monoclonal CBA and AKR autoantibodies has been characterized. These reveal a hitherto unrecognized complexity at the Thy-1 locus and evidence for intragenic control. Epitopes recognized by the autoantibodies differed in species and tissue distribution from alloantigenic determinants but their specificity was confirmed by transfection studies with the cloned Thy-1b gene. The quantitative and qualitative differences in epitope expression between Thy-1a and Thy-1b alleles were inherited as single Mendelian traits and in the absence of recombinants, suggesting translational control.

Animals↗
PubMed1986

Suicide selection of murine T helper clones specific for variable regions of the influenza hemagglutinin molecule.

A negative selection procedure has been developed to obtain murine T helper clones specific for variable regions of the influenza A hemagglutinin. T cell lines, established from mice primed by intranasal infection with X31 (H3N2) virus, were cross-stimulated with natural variant viruses of known primary sequence (either A/TEXAS/1/77 or A/ENG878/69) and proliferating cells eliminated by treatment with the cell cycle-specific drug 5-bromodeoxyuridine. After two suicide cycles, T cell lines were subtype specific and failed to recognize the natural variants. Clones were established by limiting dilution and their specificity was determined against a panel of viruses. Extensive diversity was evident in the reactivity of clones from individual donors, and two major T cell recognition sites were defined in the globular head region of the hemagglutinin molecule.

Amino Acid Sequence↗
PubMed1986

Extended wear hydrogel and daily wear hard contact lenses for aphakia. Success and complications compared in a longitudinal study.

The success and complications of extended wear hydrogel (EWSCL) and daily wear hard contact lens (DWHCL) correction for aphakia were evaluated retrospectively in two comparable groups of unilaterally aphakic patients (64 with EWSCL, 86 with DWHCL). At the end of the follow-up period, 55% of patients in each group were still using contact lenses. Suppurative keratitis occurred in two (3%) patients using EWSCL and none with DWHCL. The relative risk to all patients of a complication developing severe enough to result in a loss of wearing time was 9.8 times higher for the EWSCL users compared with the DWHCL group; this risk increased to 11.4 times for the patients still using lenses at the end of the follow-up period. The EWSCL patients had 1.9 times more visits for routine care and 5 times more unplanned visits to deal with complications than the DWHCL patients.

Aged↗
PubMed1985

Argon laser trabeculoplasty or trabeculectomy a prospective randomised block study.

A prospective randomised block study of treatment by either argon laser trabeculoplasty or trabeculectomy was undertaken in patients with chronic open angle glaucoma not controlled by medication. The study was undertaken in two centres in the United Kingdom where the regimes of medical treatment prior to interference were different. Regression analysis showed that in both populations laser trabeculoplasty was effective in reducing the intraocular pressure but it was less effective than trabeculectomy in permanently reducing the intraocular pressure to within normal limits. Laser trabeculoplasty was most effective in those patients whose intraocular pressure was initially high but many of these required post-operative medication or surgery. Laser trabeculoplasty is a useful adjunct to the therapy of open angle glaucoma but it is not a substitute for trabeculectomy as a method of permanently reducing the intraocular pressure to normal. Because of the effectiveness of both these methods of treatment we feel it no longer justified to use anything other than simple local medication to control the intraocular pressure before proceeding to active therapy.

Adult↗
PubMed1984

Surface carbohydrate epitopes of Thy-1.1 and Thy-1.2 thymocytes are distinguished by a monoclonal antibody with a specificity common to peanut agglutinin.

NIMF4-31.7 is a monoclonal IgM antibody with affinity for terminal galactose residues of membrane glycoproteins, Sepharose and agarose. It is cytotoxic for a subpopulation of murine thymocytes and peripheral lymphocytes, corresponding to the peanut agglutinin-positive population, but reacts with a majority of cells after neuraminidase treatment. It has revealed a genetic linkage between the Thy-1 locus and quantitative expression of carbohydrate determinants on the thymocyte membrane.

Animals↗