The Rhesus (Rh) D antigen is important in transfusion medicine and is the major target in haemolytic disease of the newborn (HDN). The aims of this project were to characterise the helper-T (Th) cell response that drives anti-D alloantibody production in HDN as a first step towards developing an improved or alternative strategy to the current programme of prophylaxis, based on the manipulation the T-cell response. Peripheral blood mononuclear cells (PBMC) were obtained from 22 individuals, who had developed anti-RhD alloantibodies following natural or deliberate immunisation, and from 22 RhD negative and from 12 RhD positive control donors who had not been immunised with RhD. A panel of 69 overlapping synthetic 15-mer peptides, spanning the sequence of the RhD protein, was screed for the ability to stimulate recall proliferation and cytokine production from T-cells in cultures of the PBMC. T cells from all 22 of the alloimmunised donors proliferated in response to RhD peptides and typically multiple peptides were stimulatory. In contrast, only a few minor responses were observed in the control donors. RhD peptides 6, 13, 17, and 28 were identified as immunodominant peptides that stimulated proliferation in over 50% of the alloimmunised donors. Each of these peptides were promiscuous in their ability to stimulate T-cells from donors of the common HLA allotypes in this study. Each immunodominant peptide contains multiple core epitopes and multiple sets of MHC/TCR contacts. Preliminary findings indicate that neither peptides shorter than 15mer length nor analogues can be designed to boost or tolerise alloimmunised donors. The RhD peptides induced a complex pattern of cytokine production from alloreactive T cells. Both IFN-gamma and IL-4 could be produced to the RhD peptides indicative of a Th0 response. In addition, particular peptides elicited the production of the potentially inhibitory cytokines IL-10 or TGFb and not proliferation.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:274854 |
| Date | January 2002 |
| Creators | Stott, Lisa M. |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://digitool.abdn.ac.uk/R?func=search-advanced-go&find_code1=WSN&request1=AAIU170746 |
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