Thesis (Ph. D.)--University of Missouri--Columbia, 1996. / Typescript. Vita. Includes bibliographical references (leaves: [167]-204). Also available on the Internet.

Thesis (Ph. D.)--University of Texas at El Paso, 2009. / Title from title screen. Vita. CD-ROM. Includes bibliographical references. Also available online.

Thesis (Ph. D.)--University of Hong Kong, 1993. / Cover title.

South Africa is at present encountering one of the worst Tuberculosis (TB) epidemics in the world, accentuating the need for intervention to eradicate TB. Various studies have established that certain population groups are at risk for increased susceptibility to infection with Mycobacterium tuberculosis (M. tuberculosis). This predominantly occurs in populations, like the native African population groups, who were not exposed to TB until the disease arrived in their country with European settlers, colonialists and missionaries. These population groups consequently lack the natural resistance to infection, which other populations developed through years of exposure to the pathogen. Several susceptibility-associated genetic polymorphisms have been proposed to explain differential susceptibility to TB. HLA class II molecules play a pivotal role in the activation of the host immune response against M. tuberculosis. Consequently numerous HLA class II genes have been found to be associated with TB. Among the most commonly observed associations is that of HLA-DR2 with TB, which has been observed in various population groups. Although this association has been observed to transcend ethnic barriers, inter-population variation has also been established regarding HLA-TB associations. In this study, the possible association of HLA class II polymorphisms, specifically of the HLA-DRB1, DQB1, DRB3, DRB4 and DRB5 loci, with TB susceptibility was investigated in the Venda population of South Africa. This was achieved by conducting both a case-control and family-based association study. The results obtained in this study established a unique association between HLA-DRB1*1302, DQ7 and TB susceptibility. A marginally significant association was also observed with DRB1*1301 and DQ6d and possible TB resistance. The above-mentioned results, which were observed in the case-control group, could not be replicated in the family-based study. It was therefore concluded from the results obtained in this study that employing both a case-control and family-based analysis when undertaking an association study is the most beneficial option. / Prof. Liza Bornman

published_or_final_version / Pathology / Master / Master of Philosophy

The aim of this study was to design a resolution typing system for the HLA-B gene. This technique involves a one-step PCR reaction utilizing genomic DNA and sequence-specific primers to determine the specificity of each allele and to produce a larger primer data base ideal for serological analysis. The application of this technique to serological analysis can improve serology detection which is currently hindered by antibody cross-reactivity and the unavailability of useful typing reagents.

This study describes the development and validation of mutagenized cloned DNA constructs, which correspond to the polymorphic regions of the class II region of the HLA complex. The constructs were used to verify the allelic specificity of primers and probes in polymerase chain reaction (PCR)-based HLA typing assays such as Sequence Specific Primers (SSP) and Sequence Specific Oligonucleotide Probes (SSOP). The constructs consisted of the entire polymorphic region of exon 2 of class II HLA allele sequences that included primer annealing sites or probe hybridization sites. An HLA allele sequence was inserted into a plasmid, cloned, then mutagenized to match a specific HLA allele, and finally, the correct clone was verified by bidirectional sequencing of the insert. Thus, the construct created a cloned reference DNA sample for any specific allele, and can be used to validate the accuracy of various molecular methodologies.

Xu Xuequn. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (leaves 100-125). / Abstracts in English and Chinese. / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Epstein-Barr (EBV) Virus --- p.1 / Chapter 1.1.1 --- Virus Structure and Genome Structure --- p.1 / Chapter 1.1.2 --- Virus Types --- p.2 / Chapter 1.2 --- EBV Infection and malignancies --- p.3 / Chapter 1.2.1 --- In Vitro Infection --- p.3 / Chapter 1.2.2 --- Infection in the Natural Host --- p.8 / Chapter 1.2.3 --- Malignancies Associated with EBV --- p.11 / Chapter 1.3 --- T Cell-Mediated Immune Response to EBV --- p.16 / Chapter 1.3.1 --- The Pathway of Cell-Mediated Immune Response in Viral Infection --- p.16 / Chapter 1.3.2 --- Cell-Mediated Immune Response to EBV --- p.18 / Chapter 1.3.3 --- The Feature of CTLs Response to EBV --- p.20 / Chapter 1.4 --- CTLs to EBV Relevant MalignancieśؤApplications and Challenges --- p.21 / Chapter 1.5 --- HLA Polymorphisms and Strategy of Epitope-Based CTLs Therapy --- p.24 / Chapter 1.6 --- The Effect of HLA Polymorphism on EBV-Specific CTL Epitope Choice in Southern Chinese --- p.27 / Chapter 1.7 --- ELISPOT Assay 226}0ؤ Detection of CTLs Response --- p.32 / Chapter 1.8 --- Aim of This Study --- p.37 / Chapter Chapter 2: --- Material and Methods: --- p.39 / Chapter 2.1 --- Peptides --- p.39 / Chapter 2.2 --- PBMCs Preparations --- p.43 / Chapter 2.3 --- PBMC Counting and Cells Dilution --- p.43 / Chapter 2.4 --- Elispot Assay --- p.44 / Chapter 2.5 --- Counting the Spots --- p.45 / Chapter 2.6 --- Spots Forming Cells (SFC/106) and Positive Standard --- p.46 / Chapter Chapter 3: --- Results --- p.47 / Chapter 3.1 --- Validation of ELISPOT assay methodology --- p.47 / Chapter 3.2 --- CTLs Response to Each Epitope in the Population --- p.55 / Chapter 3.2.1 --- Positive Response to A11 Restricted and Mutant Epitopes in the Population --- p.55 / Chapter 3.2.2 --- Positive Frequencies of A2 Restricted Epitopes in the Population --- p.63 / Chapter 3.2.3 --- Positive Frequencies of Other HLA Allele Restriction Peptides --- p.70 / Chapter 3.3 --- CTLs Response Frequencies Categorized by Proteins --- p.74 / Chapter 3.3.1 --- "CTLs Response to LMP1, LMP2, EBNA1 Epitopes" --- p.74 / Chapter 3.3.2 --- "CTLs Response to EBNA2, EBNA-LP Epitopes, EBNA3 Epitopes" --- p.75 / Chapter 3.3.3 --- CTLs Response to LYTIC Epitopes --- p.79 / Chapter 3.4 --- Summary --- p.80 / Chapter Chapter 4: --- Discussion --- p.82 / Chapter 4.1 --- Discussion of A11 Restricted Epitopes --- p.82 / Chapter 4.2 --- Discussion of A2 Restricted Epitopes --- p.86 / Chapter 4.3 --- Discussion of Other HLA Restricted Epitopes --- p.89 / Chapter 4.4 --- "Discussion ofLMPl, LMP2, EBNA1 Epitopes" --- p.92 / Chapter 4.5 --- "Discussion of EBNA2, EBNA3, and EBNA-LP epitopes" --- p.96 / Chapter 4.6 --- Discussion of LYTIC Epitopes --- p.96 / Chapter 4.7 --- Discussion of Summary --- p.98 / Chapter Chapter 5 --- Conclusion --- p.99 / Chapter 6 --- Reference --- p.100 / Chapter 7 --- Appendix --- p.126 / Chapter 7.1 --- "Appendix 1, raw data of Elispot assay on CTLs response to EBV relevant epitopes m Hong Kong donors" --- p.126 / Chapter 7.2 --- "Appendix 2, frequencies from highest cell number wells of the peptides (SFC/106)" --- p.126 / Chapter 7.3 --- "Appendix 3, typical Elispot assay figure " --- p.126

Although early studies on HCR provided valuable information for its characterization, the functions of HCR remain unclear. / In addition, we also isolated HCR partners in keratinocyte using a yeast two-hybrid screening. Two novel HCR partners, keratin 17 and nm23-H2, were identified. Since the expression of keratin 17 in epidermis has been recognized as a hallmark of psoriatic plaques, our findings support HCR as a candidate gene for psoriasis susceptibility. We speculate that nm23-H2 is involved in endocytosis together with HCR because nm23 also participated in endocytotic pathways. / In this study, we attempted to relate the function of HCR gene to its role in the pathogenesis of psoriasis. We first examined the subcellular localization of HCR. From a series of co-localization experiments, we eventually localized HCR in early endosomes because almost completely overlapped with active Rab4 which regulates vesicle traffic from early endosomes to perinuclear recycling endosomes and to the plasma membrane indicating that HCR may regulate sorting of internalized cargo from early endosomes to the recycling endosomes or back to the cytoplasm. / Psoriasis is a common chronic skin disorder affecting approximately 1-2% of the Caucasian population. A genetic basis for psoriasis susceptibility has been determined, however, the genetic influence of psoriasis is complex. Several genetic linkage studies have been identified. PSORS1 at 6p21.3 which has been narrowed down to a few hundred kilobase intervals around the HLA-C is the most consistently observed susceptibility locus for psoriasis in both linkage analyses and genome wide scans. HCR is a candidate gene lying within the HLA region which was previously named PG8 for 'putative gene 8' and is now more commonly called HCR for 'alpha-helix coiled-coil rod homolog'. The HCR gene is highly polymorphic. SNP association analysis showed that one SNP haplotype, named HCR*WWCC (corresponding to SNPs at nucleotides 307, 325, 1723, 2327, and involving amino acids 103, 109, 575 and 776, respectively), was associated with psoriasis. Early studies showed that the protein was confined to basal keratinocytes in healthy and non-lesional skin, whereas, it was expressed above the tips of basal and suprabasal dermal papillae in psoriatic lesional skin. / Li, Chunman. / "November 2005." / Source: Dissertation Abstracts International, Volume: 69-02, Section: B, page: 0810. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (leaves 137-149). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese. / School code: 1307.

[Truncated abstract] Natural killer (NK) cell alloreactivity can be exploited in haploidentical haematopoietic stem cell transplantation (HSCT) to improve graft survival, reduce graft versus host disease and decrease leukaemic relapse. NK cells lyse cells that have reduced expression of class I HLA molecules. In an allogeneic setting, donor NK cells may be activated by the absence of donor (self) class I HLA molecules on recipient cells; the absence of self-epitopes being detected by inhibitory KIR receptors on donor NK cells. The way in which genetic polymorphism of the receptors and ligands affects NK allorecognition of missing self, has not been fully elucidated. HLA-C molecules are divided into two groups, C1 and C2, with KIR2DL1 recognising cells expressing C2 and KIR2DL2 and KIR2DL3 recognising cells expressing C1. Donor NK cells expressing KIR2DL2 or KIR2DL3 can be alloreactive towards a recipient if they lack the C1 epitope and donor NK cells expressing KIR2DL1 can be alloreactive towards a recipient if they lack the C2 epitope. KIR3DL1 recognises the Bw4 epitope present on one-third of HLA-B alleles and certain HLA-A alleles. NK cells from donors expressing KIR3DL1 can be alloreactive towards recipients whose cells lack Bw4. Mismatches of KIR related HLA epitopes does not always results in NK alloreactivity. Therefore it is not possible to reliably predict NK alloreactivity based solely on the donor's HLA type and KIR repertoire and the recipient's HLA type. ... All Bw4-positive HLA-B alleles, with the exception of HLA-B*1301 and B*1302, protected targets from lysis. HLA-A*2402 and HLA-A*3201 unequivocally protected target cells from lysis whereas HLA-A*2501 and HLA-A*2301 provided only weak protection from lysis. KIR3DL1-dependent alloreactive NK clones were identified in donors whose only Bw4 positive allele was HLA-A*2402 but not in donors whose only Bw4 positive HLA allele was HLA-B*1301 or B*1302. Finally this thesis demonstrated that an activating KIR can control NK cell alloreactivity. Donors who are C2 negative and KIR2DS1 positive had NK cells that expressed the activating receptor KIR2DS1 and were capable of lysing cells expressing the C2 epitope. More so, KIR2DS1 dependent NK clones were shown to override inhibitory signals generated by NKG2A interacting with its ligand, HLA-E. The identification of these NK clones has important implications for haploidentical HSCT in that recipient expressing all three NK epitopes, C1, C2 and Bw4 were previously thought to be resistant to alloreactive NK cells controlled by inhibitory receptors. Such patients may be amenable to haploidentical HSCT from C2 negative, KIR2DS1 positive donors. These results will improve the ability to predict NK cell alloreactivity based on a donor's HLA type and KIR repertoire and the recipient?s HLA type.