SUMMARYVariant antigenic types (VATs) represented in a total of 47 first relapse populations of 6 clones of Trypanosoma brucei LUMP 227 were identified by immunofluorescent staining of living trypanosomes, using antiserum raised against purified surface antigens. The relative growth rates of these 6 clones were measured both individually and when grown together in a mixed population, and were found to be different under these two sets of conditions. A pattern emerged in the VATs represented in relapses of each clone, with some types being expressed more frequently than others and certain VATs being only very rarely expressed. It is suggested that new VATs are expressed according to a statistically definable order of priority which is different for each parent VAT, and that some VATs may be able to change to certain others only after passing through an intermediate VAT. The order of priority of appearance of VATs does not appear to correlate with growth rate measured either in individual clones or when clones are grown in a mixed population.

Antigenic variation in the African trypanosomes involves the sequential expression of genes coding for different variant surface glycoproteins (VSGs) (reviewed in refs 1-3). When expression of some VSG genes is switched on, a newly duplicated copy of the expressed gene has been observed within the trypanosome genome, which is not found after the gene's expression is switched off again. The duplicated copy has therefore been called an expression-linked copy (ELC). The expression of the gene appears to be strictly coupled to the presence of the ELC. This has led to the hypothesis that the duplicative transposition generating the ELC may itself be responsible for the control of VSG expression. With other VSG genes, expression-linked duplication has not been observed, and expression is clearly not controlled in this way. Data are presented here which demonstrate that either of these observations may be obtained with a single VSG gene, depending on the chance selection of particular clones from antigenically switched populations. Thus, the different observations do not imply the existence of two distinct classes of VSG gene controlled by different mechanisms, but different aspects of processes common to all VSG genes.

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Summary The C01 7-1A/GA733 antigen is associated with human carcinomas and some normal epithelial tissues. This antigen has shown promise as a target in approaches to passive and active immunotherapy of colorectal cancer. The relevance of animal models for studies of immunotherapy targeting this antigen in patients is dependent on the expression of the antigen on normal animal tissues. Immunohistoperoxidase staining with polyclonal rabbit antibodies to the human antigen revealed the human homologue on normal small intestine, colon and liver of mice, rats and non-human primates, whereas mouse monoclonal antibodies to the C01 7-1 A or GA733 epitopes on the human antigen did not detect the antigen. Polyclonal rabbit antibodies, elicited by the murine antigen homologue derived from recombinant baculovirus-infected insect cells, immunoprecipitated the antigen from mouse small intestine, colon, stomach, kidney and lung. The isolated recombinant murine protein bound polyclonal, but not monoclonal, antibodies to the human C017-1A/GA733 antigen, and recombinant human antigen bound polyclonal antibodies elicited by the murine antigen homologue. Thus, the antigen homologue expressed by animal tissues is similar, but not identical, to the human antigen. These results have important implications for experimental active and passive immunotherapy targeting the C01 7-1A/GA733 antigen.

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