Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA–viral peptide interaction as the major factor modulating durable control of HIV infection.

Radioautographic study of the binding of GAT-125I to spleen cells of genetic responder and nonresponder mice demonstrates that among mice not injected with antigen all strains have approximately the same number of antigen-binding cells; after injection with antigen the number of antigen-binding cells increases in responders but not in nonresponders. Nonresponders are shown to make antibody after injection with GAT complexed with an immunogenic carrier, demonstrating the presence of potentially functional B cells in responders and nonresponders alike. When incubated in the warm, antigen-binding cells of both responders and nonresponders concentrate antigen at one pole of the cell, forming caps.

Nitrogen dioxide (NO2) is a free radical-producing oxidant gas. Inhalation of NO2 could cause airway inflammation, and decrease immune function. This experiment tested the hypothesis that exposure to NO2 would: 1) increase leukocytes in bronchoalveolar lavage (BAL); and 2) change the distribution of lymphocyte subsets and activation in BAL and peripheral blood (PB). Using a counter-balanced, repeated-measures design, 15 healthy volunteers were exposed to filtered air (FA) or 2.0 parts per million NO2 for 4 h x day(-1) (4 x 30 min of exercise), for three consecutive days. Bronchoscopy was performed 18 h following each exposure set, and PB was drawn pre-exposure and pre-bronchoscopy. Flow cytometry was used to enumerate lymphocyte subsets and activation makers in BAL and PB. In the bronchial fraction, there was an increase in the percentage of neutrophils following NO2 exposure compared to FA (median (interquartile range): 10.6 (4.8-17.2)% versus 5.3 (2.5-8.3)%; p=0.005). In the BAL, there was a decrease in the percentage of T-helper cells following NO2 exposure compared to FA (55.9 (40.8-62.7)% versus 61.6 (52.6-65.2)%; p=0.022). For PB, there were no between-condition differences in any leukocyte or lymphocyte subsets, or activation. In conclusion exposure to nitrogen dioxide results in bronchial inflammation and a minimal change in bronchoalveolar lavage T-helper cells, and no changes in peripheral blood cells.

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A new series of 2,4-dinitrophenyllysyl oligopeptides containing a trialanyl sequence was prepared for investigation of the minimal size requirements and influence of charge density on immunogenicity and the specificity of the immune response to those defined antigens. The Lys,-Alas-N'-DnpLys series of peptides was synthesized by: (1) stepwise synthesis of the tetrapeptide P la3-N'-Dnp-Lys benzyl ester ;(2) polymerization of Ne-Z-Lys-N-carboxyanhydride using the above tetrapeptide as the initiator; (3) removal of protecting groups; and (4) fractionation of the resulting Lys,-Ala3-N'-Dnp-Lys series into its individual components by ion exchange chromatography. All inbred strain 2 guinea pigs, when immunized with the unfractionated Lys,-Alas-N'-DnpLys (a = lo), Lysc-Ala,-N'-Dnp-Lys, or Lys7-Alar-W-DnpLys, responded by the development of delayed hypersensi-S ynthetic polypeptide antigens of defined chemical structure have been useful tools of immunochemical investigation (Sela, 1970). The dinitrophenyl (Dnp)-oligolysinel system has afforded a means of studying the chemical requirements for immunogenicity as well as the specificity of antibody and of cell-mediated immunologic reactions Paul et ai., 1970;Schlossman, 1972). It was established that the minimal chain length required for immunogenicity of polylysine and Dnp-oligolysines in guinea pigs is seven Llysine residues . We wanted now to find out whether it is possible to replace some of the lysines by other amino acid residues such as alanine. A series of oligopeptides of the general chemical structure of Lys,-Ala3-Nf-Dnp-Lys was prepared. These immunogens consist of an oligolysine part of varying chain length n and of a constant part Alas-N'-Dnp-Lys. The trialanyl sequence separates the oligolysine carrier from the Dnp-lysine hapten.It was expected that if a sequence of seven lysine residues is a prerequisite for immunogenicity, the smallest member of the series to be found immunogenic will be Lys7-Ala3-NC-Dnp-Lys.If, however, one, two, or three of the lysine residues can be

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