Biomedical subjects

B Nepom

Publications and source records attributed to B Nepom.

5 recordsLinked to original sources

PubMed1997

Epstein-Barr virus uses HLA class II as a cofactor for infection of B lymphocytes.

Infection of B lymphocytes by Epstein-Barr virus (EBV) requires attachment of virus via binding of viral glycoprotein gp350 to CD21 on the cell surface. Penetration of the cell membrane additionally involves a complex of three glycoproteins, gH, gL, and gp42. Glycoprotein gp42 binds to HLA-DR. Interference with this interaction with a soluble form of gp42, with a monoclonal antibody (MAb) to gp42, or with a MAb to HLA-DR inhibited virus infection. It was not possible to superinfect cells that failed to express HLA-DR unless expression was restored by transfection or creation of hybrid cell lines with complementing deficiencies in expression of HLA class II. HLA class II molecules thus serve as cofactors for infection of human B cells.

Antibodies, Monoclonal↗

PubMed1996

Modulation of HLA-DQ binding properties by differences in class II dimer stability and pH-dependent peptide interactions.

Intermolecular interactions between peptides and class II molecules intracellularly are likely to be influenced by different pH conditions in different endosomal compartments. We compared the pH-dependent binding of peptides to HLA-DQ alleles 3.1 and 3.2, two well-studied human class II molecules with limited structural variability but different genetic associations with autoimmune diseases. Binding of the "promiscuous" binding peptide 34P3A as well as that of several allele-specific peptides were optimal for DQ3.2 at relatively acidic pH, compared with DQ3.1, with a pH optimum for DQ3.2 at pH 5.5 and for DQ3.1 at pH 6.5. A specific polymorphism at residue 57 of the DQ molecule accounted for some, but not all, of this difference. When the intrinsic stability of the class II dimer was assessed using partially denaturing gel electrophoresis after incubation at different pH, the DQ3.2 molecule demonstrated relative instability at neutral pH compared with DQ3.1, again suggesting a preference for peptide binding at relatively acidic conditions for HLA-DQ3.2. Interestingly, this preference for binding at acidic pH was not found for a class II-associated invariant chain peptide. Intrinsic alphabeta dimer stability and the pH optima for peptide binding studied in this report are likely to be significant determinants for allelic differences in DQ binding profiles in vivo.

Alleles↗

PubMed1995

Deficient antigen-presenting cell function in multiple genetic complementation groups of type II bare lymphocyte syndrome.

The absence of HLA class II gene expression in type II bare lymphocyte syndrome (BLS) results from defective transcriptional activation of class II histocompatibility genes. Genetic studies have revealed that distinct defects in multiple trans-acting factors result in the immunodeficient BLS phenotype. We studied antigen-presenting cell (APC) function in DR-transfected BLS cells derived from multiple complementation groups. Each BLS cell line displayed the same defective APC phenotype: an inability to mediate class II-restricted presentation of exogenous protein antigens, and structurally altered class II alpha beta dimers. Expression of the HLA class II-like genes DMA and DMB, previously implicated in antigen presentation, was reduced or absent in the BLS cells. Fusion of BLS cells with cell line 721.174, which has a genomic deletion of HLA class II genes, coordinately restores class II structural gene and DM gene expression and a wild-type APC phenotype. Thus each of the molecular defects that silences class II structural gene transcription also results in a defective APC phenotype, providing strong evidence for coregulation of these two functionally linked pathways.

Amino Acid Sequence↗

PubMed1991

The immunogenetics of juvenile rheumatoid arthritis.

Recent major advances in understanding the genetic structure of the human leukocyte antigen (HLA) region and how HLA molecules contribute to immune responses have been paralleled by more precise identification of specific HLA genes conferring susceptibility to the various forms of juvenile rheumatoid arthritis (JRA). This article presents current models for HLA-associated autoimmune disease susceptibility and summarizes the HLA Class II alleles currently known to be associated with JRA: primarily DR8, DR5, DR6, and DPw2.1 in pauciarticular onset JRA; and DR4 in rheumatoid factor-positive polyarticular onset JRA. Rheumatoid factor-negative polyarticular onset JRA and systemic onset JRA are variously associated with several of these same genes. Gene interactions and the clinical utility of HLA typing in this disease are also discussed.

Antibody Formation↗

PubMed1991

Psychosomatic musculoskeletal pain in childhood: clinical and psychological analyses of 100 children.

The clinical and psychological findings on 100 children with psychosomatic musculoskeletal pain seen at a major pediatric rheumatology referral center are reported. Most (76%) were female, median age was 13 years, and median duration of symptoms was 1 year. Multiple painful sites were common (66%). The pain was constant (63%) or intermittent (37%); 45% had hyperesthesia, and almost all maintained a cheerful affect when complaining of severe pain. Two predominant abnormal family milieu were seen. One was cohesive, stable, and organized, but intolerant of separation and individuation. The other was chaotic, emotionally unsupportive, with high levels of conflict. Members of the cohesive family type reported significantly less distress than members of chaotic families. Enmeshment between mother and child was common in both family types. Although frequently viewed as bright, most of these children had normal intelligence, and some had unrecognized academic difficulty. These children, compared with those with arthritis, had a significantly lower global well-being score. Clinical depression was unusual (11%). Most (97%) responded favorably to intensive physical and occupational therapy along with individual or family psychotherapy; 78% become symptom free or fully functional. Children with these signs and symptoms should have full psychological evaluations and respond well to treatment directed toward decreasing pain and restoring function.

Adolescent↗