Histocompatibility typing by cellular radioimmunoassay

Longenecker, B. M.; Singh, Bhagirath; Gallatin, Michael; Havele, Calliopi

doi:10.1007/bf01844008

Cited by 14 publications

(9 citation statements)

References 16 publications

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“…consequence might be that the class I molecules in chicken MHC heterozygotes could receive peptides not available in homozygotes. In fact, we find that the expression level of class I molecules in B15/B21 heterozygotes is increased compared with B15/B15 homozygotes, similar to a study buried in the scientific literature (22). As previously suggested (16,26), TAP polymorphism may increase the peptides available in heterozygotes compared with homozygotes, and thus can add another molecular layer to selection by heterozygote advantage (overdominance) determined by the chicken MHC.…”

Section: Discussionsupporting

confidence: 89%

“…Overall, it seems likely that the cell surface expression of B15 class I molecules in B15/B21 heterozygotes increases beyond the levels of B15/B15 homozygotes, although from these experiments, we cannot rule out that the minor B21 molecule BF1*2101 or another unidentified class I molecule has increased in amount. These data are similar to results of radioimmunoassays using alloantisera for B15 and B21 class I molecules reported long ago (22).…”

Section: Significancesupporting

confidence: 91%

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Surface expression, peptide repertoire, and thermostability of chicken class I molecules correlate with peptide transporter specificity

Tregaskes

Harrison

Sowa

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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The chicken major histocompatibility complex (MHC) has strong genetic associations with resistance and susceptibility to certain infectious pathogens. The cell surface expression level of MHC class I molecules varies as much as 10-fold between chicken haplotypes and is inversely correlated with diversity of peptide repertoire and with resistance to Marek's disease caused by an oncogenic herpesvirus. Here we show that the average thermostability of class I molecules isolated from cells also varies, being higher for high-expressing MHC haplotypes. However, we find roughly the same amount of class I protein synthesized by high-and low-expressing MHC haplotypes, with movement to the cell surface responsible for the difference in expression. Previous data show that chicken TAP genes have high allelic polymorphism, with peptide translocation specific for each MHC haplotype. Here we use assembly assays with peptide libraries to show that high-expressing B15 class I molecules can bind a much wider variety of peptides than are found on the cell surface, with the B15 TAPs restricting the peptides available. In contrast, the translocation specificity of TAPs from the low-expressing B21 haplotype is even more permissive than the promiscuous binding shown by the dominantly expressed class I molecule. B15/B21 heterozygote cells show much greater expression of B15 class I molecules than B15/B15 homozygote cells, presumably as a result of receiving additional peptides from the B21 TAPs. Thus, chicken MHC haplotypes vary in several correlated attributes, with the most obvious candidate linking all these properties being molecular interactions within the peptideloading complex (PLC).ABC transporter | restrictive | permissive | heterozygous advantage | overdominance

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Section: Discussionsupporting

confidence: 89%

Section: Significancesupporting

confidence: 91%

Surface expression, peptide repertoire, and thermostability of chicken class I molecules correlate with peptide transporter specificity

Tregaskes

Harrison

Sowa

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…Anti-TNP antibody titers in the sera of immunized animals were measured by the cellular radioimmunoassay of Longenecker et al [22] utilizing trinitrophenylated and control unconjugated SRBC.…”

Section: Cellular Radioimmunoassaymentioning

confidence: 99%

Tolerance induction during ontogeny II. Distinct unresponsive states in immature mice question the generality of clonal abortion

Waters

Diener

1983

Eur J Immunol

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Multivalent trinitrophenyl (TNP) conjugates of both human gamma-globulin (HGG) and bovine serum albumin (BSA) are capable of inducing hapten-specific unresponsiveness in neonatal mice, as assessed by challenge with TNP on thymus-dependent carriers. When such mice are challenged with TNP on thymus-independent carriers, however, only TNP-HGG- but not TNP-BSA-treated mice are found to be substantially unresponsive to the hapten. Moreover, unresponsiveness induced by BSA, but not HGG, as a carrier was associated with the presence of antigen-specific suppressor cells. Thus, contrary to predictions made by defendants of the classical clonal abortion hypothesis, functional deletion of hapten-specific B cells appears to depend on the nature of the hapten-carrier complex. This conclusion is supported by B cell-precursor frequency estimates indicating that the number of hapten-specific precursor cells is significantly lower in TNP-HGG-treated mice, but remains unaltered in TNP-BSA-treated mice relative to the precursor frequency in untreated animals. While it remains a formal possibility that the differences in tolerogenicity seen between the two carriers can be interpreted in terms of a difference in serum half-life, we favor the interpretation that the distinction lies in molecular aspects of the carrier, which allow for differences in antigen handling by sets of interacting cells.

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“…Although the B21 TAPs do not pump as diverse peptides as TAPs from typical mammals, it seems likely that they provide would peptides for some more fastidious class I molecules, as might be found in certain heterozygotes. For instance, the expression level of B15 molecules increases markedly in B15/B21 heterozygotes compared to B15/B15 homozygotes (, J. Kaufman, unpublished data). As suggested , this result may give a deeper meaning to the notion of heterozygous advantage and overdominance.…”

Section: Peptide Repertoire and Cell Surface Expression Level Of Chicmentioning

confidence: 99%

Co‐evolution with chicken class I genes

Kaufman

2015

Immunological Reviews

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The concept of co-evolution (or co-adaptation) has a long history, but application at molecular levels (e.g., 'supergenes' in genetics) is more recent, with a consensus definition still developing. One interesting example is the chicken major histocompatibility complex (MHC). In contrast to typical mammals that have many class I and class I-like genes, only two classical class I genes, two CD1 genes and some non-classical Rfp-Y genes are known in chicken, and all are found on the microchromosome that bears the MHC. Rarity of recombination between the closely linked and polymorphic genes encoding classical class I and TAPs allows co-evolution, leading to a single dominantly expressed class I molecule in each MHC haplotype, with strong functional consequences in terms of resistance to infectious pathogens. Chicken tapasin is highly polymorphic, but co-evolution with TAP and class I genes remains unclear. T-cell receptors, natural killer (NK) cell receptors, and CD8 co-receptor genes are found on non-MHC chromosomes, with some evidence for co-evolution of surface residues and number of genes along the avian and mammalian lineages. Over even longer periods, co-evolution has been invoked to explain how the adaptive immune system of jawed vertebrates arose from closely linked receptor, ligand, and antigen-processing genes in the primordial MHC.

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Histocompatibility typing by cellular radioimmunoassay

Cited by 14 publications

References 16 publications

Surface expression, peptide repertoire, and thermostability of chicken class I molecules correlate with peptide transporter specificity

Surface expression, peptide repertoire, and thermostability of chicken class I molecules correlate with peptide transporter specificity

Tolerance induction during ontogeny II. Distinct unresponsive states in immature mice question the generality of clonal abortion

Co‐evolution with chicken class I genes

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