The hallmark of the classical major histocompatibility complex (MHC) class I molecules is their astonishing level of polymorphism, a characteristic not shared by the nonclassical MHC class I genes. A distinct family of MHC class I genes has been recently identified within the human MHC class I region. The MICA (MHC class I chain-related A) gene in this family is a highly divergent member of the MHC class I family and has a unique pattern of tissue expression. We have sequenced exons encoding the extracellular alpha1, alpha2, and alpha3 domains of the MICA gene from twenty HLA homozygous typing cell lines and four unrelated individuals. We report the identification of eleven new alleles defined by a total of twenty-two amino acid substitutions. Thus, the total number of MICA alleles is sixteen. Interestingly, a tentative superimposition of MICA variable residues on the HLA-A2 structure reveals a unique pattern of distribution, concentrated primarily on the outer edge of the MICA putative antigen binding cleft, apparently bordering an invariant ligand binding site.
This study provides a link between stress and initiation of inflammatory attacks in patients with FMF. REDD1 emerges as a regulator of neutrophil function upstream to pyrin, is involved in NET release and regulation of IL-1β, and might constitute an important piece in the IL-1β-mediated inflammation puzzle.
The general principles underlying protein requirements are outlined and daily allowances for protein are derived appropriate to the various age and sex population subgroups of the United States. Median body weights are however used for all age groups of the population rather than the desirable body weights used previously for adults. Following the recommendations of the FAO/WHO/UNU international working group, the protein requirement for male and female adults was taken as 0.6 g.kg-1.d-1 of high-quality highly digestible protein. By use of an age-specific scoring system and the mean amino acid composition and digestibility of the US diet, this allowance became 0.83 g.kg-1.d-1 of mixed US dietary protein--a value similar to the previous RDA but derived in a different manner. Tabulated daily protein allowance data are presented for reference age and sex groups for the US population (child-adult) together with the additional needs of pregnancy and lactation.
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