Frequency analysis of HLA-specific cytotoxic T lymphocyte precursors in humans.

Frequencies of HLA class 1-specific cytotoxic T lymphocyte precursors (CTLp) from 33 responders were determined in 115 responder/stimulator combinations. In each combination there was a single HLA-A or HLA-B antigen mismatch. A wide range of CTLp frequency (CTLpf) values was found for most A and B locus antigens. Some A locus antigens appeared less immunogenic than other A locus antigens. The effect of additional C locus differences was negligible. The relationship between responder and stimulator HLA antigens is of minor importance because HLA-specific CTLpf against crossreactive (CREG) and subtype antigens were not significantly lower than CTLpf against non-CREG antigens. The CTLpf did not correlate with Bw4 or Bw6 mismatches. The existence of a broad range of values for HLA class I-specific CTLpf is of general interest. We have arbitrarily subdivided the CTLpf values into high, medium, low, and very low. In about 20% of the combinations the HLA-specific CTLpf were low or not even detectable in our assay. In contrast, HLA-specific CTLpf in combinations with multiple HLA antigen differences were regularly high. Our results confirm the high values of allospecific CTLpf in general but simultaneously point to unexpected variations. Frequency analysis of HLA-specific CTLp may be considered a new parameter in clinical transplantation for the selection of appropriate donor/recipient pairs.

Variations in the T-cell repertoire against HLA antigens in humans.

Allospecific anti-HLA class I antigen cytotoxic T-lymphocyte precursor frequencies (CTLpf) have been estimated in peripheral blood of healthy blood donors with responder stimulator combinations mismatched for one HLA-A,B antigen. The CTLpf ranged from 1 in 400 to 1 in 10,000, with most frequent values of 1 in 600 to 4000. The following observations were made: (1) CTLpf against the same HLA antigen vary among different responders; (2) CTLpf of one responder against various HLA antigens may be different; (3) "narrow" responders produce cytotoxic T lymphocytes that recognize only the private (stimulator) alloantigen, while "broad" responders produce mainly broadly cross-reactive cytotoxic T lymphocytes with public specificity. Split-well analysis shows that very few cytotoxic T lymphocytes of "broad" responders recognize the private alloantigen only. These individual variations are not dependent on the HLA phenotype, because they also occurred in unrelated HLA-identical responders stimulated against the same mismatched stimulator cells.

Chemotactic attraction of infective hookworm larvae of Ancylostoma caninum by a dog serum factor.

Infective hookworm larvae of Ancylostoma caninum showed chemotaxis on agar plates in a dog serum gradient. This chemotactic behaviour remain unaltered using an ultrafiltrated serum fraction with a molecular weight less than 500. Gelfiltration of this ultrafiltrated fraction revealed a factor with a molecular weight of 480 causing chemotaxis. The chemotactic activity of the factor was destroyed after a pronase treatment. We conclude that the factor could be a polypeptide.

Cytopathic effects of non-syncytium-inducing and syncytium-inducing human immunodeficiency virus type 1 variants on different CD4(+)-T-cell subsets are determined only by coreceptor expression.

In peripheral blood mononuclear cells, syncytium-inducing (SI) human immunodeficiency virus type 1 (HIV-1) infected and depleted all CD4(+) T cells, including naive T cells. Non-SI HIV-1 infected and depleted only the CCR5-expressing T-cell subset. This may explain the accelerated CD4 cell loss after SI conversion in vivo.

Effect of a Tyr-to-His point-mutation at position 59 in the alpha-1 helix of the HLA-B27 class-I molecule on allospecific and virus-specific cytotoxic T-lymphocyte recognition.

HLA-B2703, a mutation of HLA-B2705, is characterized by a Tyr-to-His substitution at position 59 in the alpha 1 domain of the class-I heavy chain. So far, the HLA-B2703 subtype was found only in two Black individuals and it is the first polymorphism at position 59 of MHC class-I molecules. We have examined whether the single amino-acid substitution at position 59 results in an alloantigenic determinant and HLA-restriction element, and whether HLA-B2703 functionally differs from HLA-B2705. In vitro, HLA-B2703-positive lymphocytes were not stimulated by HLA-B2705-positive cells. Nevertheless, HLA-B2703 was recognized as an alloantigen. HLA-B2702-anti-HLA-B2705 CTL lysed HLA-B2703-positive cells less efficiently than HLA-B2705-positive cells. In addition, anti-HLA-B27 antibodies were found that lysed HLA-B2705 but not HLA-B2703 positive cells. Also, CTL clones have been described that can distinguish HLA-B2703 from HLA-B2705 (1). However, the HLA-B2703 subtype did not function as a private virus restriction element. HLA-B2705-restricted influenza virus-specific CTL also recognized HLA-B2703-positive virus-infected cells, and vice versa. Thus, the HLA-B2703 mutation represents an example of a class-I antigen without specific significance for the recognition of viral peptides.