Nomenclature for factors of the HLA system, 2004

Marsh, Steven G.E.; Albert, E. D.; Bodmer, W F; Bontrop, Ronald E.; Dupont, Bo; Erlich, Henry A.; Geraghty, Daniel E.; Hansen, John A.; Hurley, Carolyn Katovich; Mach, Bernard; Mayr, W. R.; Parham, Peter; Petersdorf, Effie W.; Sasazuki, Takehiko; Schreuder, G. M. T.; Strominger, Jack L.; Svejgaard, A.; Terasaki, Paul I.; Trowsdale, John

doi:10.1111/j.1399-0039.2005.00379.x

Cited by 631 publications

(660 citation statements)

References 99 publications

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“…HLA at A and B loci was typed at the Puget Sound Blood Center, Seattle, Washington. When 2 digits followed by xx or 4 digits are reported, low or high resolution typing was done and the old nomenclature used (73). HLA-C was typed by Dan Geraghty at the Fred Hutchinson Cancer Research Center by sequencing exons 2 and 3.…”

Section: Methodsmentioning

confidence: 99%

Cross-presentation and genome-wide screening reveal candidate T cells antigens for a herpes simplex virus type 1 vaccine

Jing¹,

Haas²,

Chong³

et al. 2012

J. Clin. Invest.

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Herpes simplex virus type 1 (HSV-1) not only causes painful recurrent oral-labial infections, it can also cause permanent brain damage and blindness. There is currently no HSV-1 vaccine. An effective vaccine must stimulate coordinated T cell responses, but the large size of the genome and the low frequency of HSV-1-specific T cells have hampered the search for the most effective T cell antigens for inclusion in a candidate vaccine. We have now developed what we believe to be novel methods to efficiently generate a genome-wide map of the responsiveness of HSV-1-specific T cells, and demonstrate the applicability of these methods to a second complex microbe, vaccinia virus. We used cross-presentation and CD137 activation-based FACS to enrich for polyclonal CD8 + T effector T cells. The HSV-1 proteome was prepared in a flexible format for analyzing both CD8 + and CD4 + T cells from study participants. Scans with participant-specific panels of artificial APCs identified an oligospecific response in each individual. Parallel CD137-based CD4 + T cell research showed discrete oligospecific recognition of HSV-1 antigens. Unexpectedly, the two HSV-1 proteins not previously considered as vaccine candidates elicited both CD8 + and CD4 + T cell responses in most HSV-1-infected individuals. In this era of microbial genomics, our methods -also demonstrated in principle for vaccinia virus for both CD8 + and CD4 + T cells -should be broadly applicable to the selection of T cell antigens for inclusion in candidate vaccines for many pathogens. IntroductionHerpes simplex virus type 1 (HSV-1) infects 60% of the US population and has a significant cumulative health care burden in addition to causing painful recurrent oral-labial infections. For example, brain and eye infections can cause permanent damage or blindness (1). HSV-1 also causes approximately 50% of clinical first-episode genital herpes in the United States. Vaccines for HSV that have been tested thus far have failed in clinical trials, including a recent phase III trial of an adjuvanted glycoprotein D (gD2) product (2). This vaccine elicits antibody and CD4 + T cell responses but fails to induce CD8 responses. Newer platforms can elicit CD8 + and CD4 + cells, but they require rationally selected T cell antigens. We therefore developed methods to permit measurement of both CD8 and CD4 responses to the complete HSV-1 proteome to begin rational prioritization of next-generation vaccine candidates.Several recent observations support the concept that an effective HSV vaccine will need to induce coordinated CD8 + and CD4 + T cell responses. HSV-1-specific CD8 + T cells localize to the site of HSV-1 infection in human and murine trigeminal ganglia (TG) (3-5), and both HSV-specific CD8 + and CD4 + T cells localize to acute and healed sites of skin infection in mice and humans, sug-

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Section: Methodsmentioning

confidence: 99%

Cross-presentation and genome-wide screening reveal candidate T cells antigens for a herpes simplex virus type 1 vaccine

Jing¹,

Haas²,

Chong³

et al. 2012

J. Clin. Invest.

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“…The MHC class I genes of human and rhesus macaque have been investigated thoroughly by various methods. In humans, the classical HLA-A, -B, and -C genes are restricted to a single locus, and are characterized by extensive polymorphism [14]. In the rhesus macaque, the homologs of HLA-A and -B, designated Mamu-A and -B respectively, are present, while the ortholog of HLA-C is absent [15].…”

mentioning

confidence: 99%

The extreme plasticity of killer cell Ig‐like receptor (KIR) haplotypes differentiates rhesus macaques from humans

et al. 2011

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NK cells are essential in shaping immune responses and play an important role during pregnancy and in controlling infections. Killer cell immunoglobulin-like receptors (KIRs) educate the NK cell and determine its state of activation. Our goal was to determine how the KIR repertoire of the rhesus macaque (Macaca mulatta) has been shaped during evolution. The presence or absence of 22 KIR gene groups was determined in 378 animals. Some unexpected observations were made in an outbred colony comprising animals of different origins. For instance, the KIR region appears to be highly plastic, and an unprecedented number of genotypes and haplotypes was observed. In contrast to humans, there is no distinction between group A and B haplotypes in the rhesus macaque, suggesting that different selective forces may be operative. Moreover, specific genes appear to be either present or absent in animals of different geographic origins. This extreme plasticity may have been propelled by co-evolution with the rhesus macaque MHC class I region, which shows signatures of expansion. The mosaic-like complexity of KIR genotypes as observed at the population level may represent an effective strategy for surviving epidemic infections. [3] but they are also involved with the vascularisation process during placentation, and thus contribute to reproductive success [4]. The education and activation state of the NK-cell is determined by the interactions of its receptors with their cognate ligands [5]. It is the shift in equilibrium of inhibitory and activating receptor signaling that ultimately leads to NK-cell activation in the form of cytokine production, cytotoxicity, or priming of the adaptive immune system [6].Killer cell immunoglobulin-like receptors (KIRs) may influence this balance through interactions with their ligands, the MHC molecules, which are called human leukocyte antigens 2719(HLA) in humans. Since both the HLA system and the KIR gene complex are characterized by variation in locus content, and segregate independent of each other, the potential array of interactions can vary considerably between individuals. Understanding the evolution and complexity of these receptor systems has broad medical relevance, since particular combinations of KIR and HLA alleles are associated with the outcome of viral infection, relapse of leukemia after transplantation, susceptibility to autoimmune disease, and successful pregnancy [7][8][9][10]. Because of its close evolutionary relationship to humans, and evidenced by similar immunological responses, the rhesus macaque (Macaca mulatta) is an important animal model to study the onset, progression, and outcome of infectious diseases, experimentally induced autoimmunity, and transplantation [11][12][13]. Moreover, certain human pathogens or their simiantrophic family members have adapted to primates as their natural host, and may show a host-specific pathology. Since in an experimental setting the onset of disease or the actual challenge with a pathogen can be controlled, it is possible to stu...

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“…17 Alleles for the individual HLA-class II loci are inherited in specific combinations called haplotypes. Haplotypes are the result of the known strong linkage disequilibrium between the HLA-DR and DQ subregions, which has been documented in many studies of outbred populations.…”

Section: Hla Nomenclaturementioning

confidence: 99%

HLA‐class II haplotype associations with ovarian cancer

Kübler

Arndt

Wardelmann

et al. 2006

Intl Journal of Cancer

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The development of cancer is a multistep process that is characterized by the accumulation of genetic alterations in cells and changed cellular interactions with the surrounding healthy tissues. The human immune system is believed to be intrinsically involved in this process. The correlation of certain human leukocyte antigen (HLA)-class I and II haplotypes with tumorigenesis is documented in a variety of tumors. However, few data exist on the possible association of specific HLA-class II alleles or haplotypes with ovarian cancer. In our sample of 52 Caucasian patients with primary ovarian carcinoma and 239 female healthy local controls, we observed a significantly increased incidence of the HLA-class II haplotypes DRB1*0301 -DQA1*0501 -DQB1*0201 (p < 0

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Nomenclature for factors of the HLA system, 2004

Cited by 631 publications

References 99 publications

Cross-presentation and genome-wide screening reveal candidate T cells antigens for a herpes simplex virus type 1 vaccine

Cross-presentation and genome-wide screening reveal candidate T cells antigens for a herpes simplex virus type 1 vaccine

The extreme plasticity of killer cell Ig‐like receptor (KIR) haplotypes differentiates rhesus macaques from humans

HLA‐class II haplotype associations with ovarian cancer

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