Class II human leukocyte antigen gene polymorphisms, cell surface expression and immunoglobulin E mediated disease

Standring, Peter (1998) Class II human leukocyte antigen gene polymorphisms, cell surface expression and immunoglobulin E mediated disease. University of Southampton, Doctoral Thesis.

Abstract

The thesis investigates the role of Human Leukocyte Antigen (HLA) class II molecules in the development of specific immunoglobulin E (sIgE) mediated responses in atopic asthmatic individuals and their relatives. Two aspects were investigated with respect to specific IgE production. The first was the role of the extensive allelic polymorphisms which involve the peptide binding site of HLA class II molecules on antigen presenting cells. The second was the role of surface expression of class II molecules. The investigations were performed on individuals of family pedigrees with two or more generations of asthma. The initial study characterised individuals from family pedigrees for their atopic disease phenotype, their production of specific IgE to a panel of six common local aero-allergens and their HLA class II type. A total of 20 family pedigrees were recruited comprising 176 individuals. The presence of asthma, atopic eczema and allergic rhinitis was determined by a standardised and validated questionnaire for disease definition. Examination of the phenotype showed a very strong association between the atopic diseases. Interestingly, although strong associations were seen between asthma, rhinitis and the production of specific IgE, there was no association with atopic eczema and specific IgE production. Furthermore there was a strong association, unconfounded by allergic rhinitis and sIgE, between asthma and atopic eczema.

HLA class II typing was performed for the following loci: DRB1, DQA1, DQB1, DPA1 and DPB1.

The results of this study suggest that within the context of asthma family pedigrees DRB1 and DPA1 alleles may be involved in the immunopathology of atopy and asthma. Evidence for an antigen epitope capture mechanism as has been investigated previously was not strongly supported by this study. An alternative mechanism involving levels of antigen presentation, as determined by HLA class II molecule density showed no clear results but this may be more important during the early development of the allergic response at the site of the first or subsequent antigen exposure.

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