呼吸道合胞病毒对致敏小鼠气道炎症和CD8+ T细胞功能的影响

目的观察呼吸道合胞病毒（RSV）对致敏小鼠气道炎症和CD8^＋T细胞功能的影响.方法BALB/c小鼠40只,随机分成4组,分别为磷酸盐缓冲液（PBS）对照组、鸡卵白蛋白（OVA）组、RSV组、OVA/RSV组;应用OVA腹腔注射致敏、OVA气道雾化结合RSV滴鼻激发哮喘;支气管肺泡灌洗液（BALF）作细胞分类计数;酶联免疫吸附试验（ELISA）测定BALF上清中白细胞介素（IL）-4、IL-5、干扰素（IFN）-γ含量;苏木精-依红（HE）染色观察肺病理变化;采用三色光流式细胞分析法测定气管旁淋巴结（PBLN）中CD4^＋、CD8^＋T细胞及细胞内细胞因子IFN-γ、IL-4、IL-5表达与TH2/TH1、Tc2/Tc1比值变化.结果（1）BALF中细胞总数及分类：与OVA组比较,OVA/RSV组细胞总数、嗜酸性粒细胞、淋巴细胞均明显增加（分别P＜0.01）;与RSV组比较,OVA/RSV组细胞总数、嗜酸性粒细胞明显增加（分别P＜0.01）.（2）BALF上清中细胞因子含量：与OVA组比较,OVA/RSV组IFN-γ、IL-4、IL-5含量均明显升高（分别P＜0.01）;与RSV组比较,OVA/RSV组IFN-γ无明显变化,而IL-4、IL-5显著上升（分别P＜0.01）.（3）肺组织病理：OVA/RSV组与其他各组比较气道黏膜增厚,管腔狭窄、收缩,上皮破坏,管壁周围炎症细胞浸润明显加重.（4）PBLN中CD4^＋（WN-γ^＋、IL-4^＋、IL-5^＋）、CD8^＋（IFN-γ^＋、IL-4^＋、IL-5^＋）T细胞各占CD3^＋T细胞百分比及TH2/TH1、Tc2/Tc1比值变化：与OVA组比较,OVA/RSV组CD8^＋（IFN-γ^＋、IL-4^＋、IL-05^＋）T细胞百分比、Tc2/Tc1比值增加（分别P＜0.01）,TH2/TH1比值无明显变化.与RSV组比较,OVA/RSV组CD4^＋（IL-4^＋、IL-5^＋）T细胞、TH2/TH1比值、CD8^＋（IL-4^＋、IL-5^＋）T细胞、Tc2/Tc1比值均明显上升（分别P＜0.01）.结论（1）OVA致敏小鼠RSV感染后可明显加重气道炎症,TH2、TH1型炎症均加强,且以TH2型炎症加重为主.（2）OVA致敏小鼠RSV感染后可引起CD8^＋T细胞数量及功能改变,即由产生IFN-γ^＋为特征的Tc1细胞向产生IL-4^＋、IL-5^＋为特征Tc2细胞转化,并可能与气道内IL-4、IL-5升高及嗜酸性粒细胞的大量募集有关.     

抗γc单克隆抗体联合供者特异性输注延长移植物存活

目的 探讨抗γ公共链单克隆抗体(抗γc单抗)联合供者脾细胞特异性输注(DST)诱导移植物长期存活的可行性及相关机制.方法 建立小鼠颈部异位心脏移植模型,组Ⅰ为单纯实施心脏移植组,组Ⅱ于移植前给予DST,组Ⅲ术前予DST联合抗γc单克隆抗体处理,术后观察移植物的存活时间及相关指标.结果 组Ⅲ心脏移植物平均存活时间明显长于组Ⅰ及组Ⅱ (P＜0.05).FACS分析显示组Ⅲ受者脾细胞中Tr比例较组Ⅰ及组Ⅱ显著增高(P＜0.05),同时脾细胞增殖活性明显减低(P＜0.05).结论 抗γ公共链单克隆抗体联合DST通过增加供者体内Tr的比例,减低对同种抗原的应答能力,显著延长同种心脏移植模型中移植物存活时间.     

恶性淋巴瘤患者TH 1/TH 2细胞因子表达水平的研究

目的 探讨恶性淋巴瘤患者血清中TH1/TH2细胞因子变化及其临床意义,为肿瘤的免疫治疗提供实验依据.方法 用流式细胞小球微阵列术(cytometric bead array,CBA)检测92例恶性淋巴瘤患者及70例健康人群血清中γ干扰素(IFN-γ)、肿瘤坏死因子-α仪(TNF-α)、白细胞介素(IL-2、IL-4、IL-5、IL-10)表达水平.结果 92例恶性淋巴瘤患者血清中TH1型细胞因子的水平分别为:IFN-γ(34.26±33.4g)pg/ml、TNF-α(8.17±10.09)pg/ml、IL-2(3.74 4±1.72)pg/ml;TH2型细胞因子的水平分别为:IL-10(6.28±8.56)pg/ml、IL-5(3.53±3.20)pg/ml、IL-4(6.22±7.13)pg/ml.除TNF-α表达水平降低外,其余5项均明显高于健康体检组,差异有统计学意义(P＜0.01).TH1细胞因子IL-2与TH2细胞因子IL-4的比值明显下降(0.78±O.44),与健康体检组(1.09±0.45)比较差异有统计学意义(P＜0.01).IL-10与疾病的进展相关,Ⅲ/Ⅳ期恶性淋巴瘤患者的表达水平为(9.58±13.96)pg/ml,Ⅰ/Ⅱ期的表达水平为(4.77±3.50)pg/ml,二者比较差异有统计学意义(P＜0.01).IFN-γ在大于60岁的恶性淋巴瘤患者中表达水平明显降低,与其他年龄段恶性淋巴瘤患者比较差异有统计学意义(P ＜0.05).结论 恶性淋巴瘤患者血清中TH1/TH2细胞因子平衡失调,检测TH1/TH2细胞因子可作为评价淋巴瘤临床进展及预后指标.TH1/TH2平衡向TH2方向漂移,这可能是肿瘤细胞发生免疫逃逸,从而导致肿瘤的发生或者转移的原因之一.     

供体骨髓输注减轻同种肝移植排斥反应

目的:研究非清髓性骨髓移植在同种肝移植免疫反应中的作用及其意义。 方法:动物实验为同种大鼠肝移植：Ⅰ组为Wistar→Wistar同基因对照组；Ⅱ组为SD→Wistar急性排斥组；Ⅲ组为SD→Wistar环孢素A（cyclosporine A,CsA）肌肉注射处理组；Ⅳ组为SD→Wistar术前1周大剂量供体骨髓细胞输注处理组。用术后一般状态、生存时间、病理学排斥分级、肝标本中IL-2、IFN-γ的表达以及胸腺内嵌合体的检测等手段，确定不同处理组移植后的排斥反应情况及机体的免疫状态。 结果:Ⅰ组大鼠术后无排斥反应发生；Ⅱ组大鼠术后9-13 d内全部死亡，中位存活时间（10.7±0.5）d，排斥反应明显；Ⅲ组大鼠仅见轻度排斥；Ⅳ组自然存活亚组6只大鼠4只长期存活 (>100 d)，排斥分级明显低于Ⅱ组（P<0.05）,与Ⅱ组相比，Ⅳ组IL-2、IFN-γ蛋白的表达均明显下调。在骨髓输注15 d后，用PCR法在雌性Wistar大鼠受体胸腺内可检测到雄性SD大鼠供体特异性的Y染色体（Y-chromosome-specific sequence，Sry）基因片段。 结论:供体骨髓输注可形成供受体细胞的嵌合状态，可降低同种异体肝移植的排斥反应，延长受体生存时间。     

TIM基因家族在免疫和疾病中的作用

初始CD4^＋T细胞经抗原刺激活化使它分化成两类功能不同的亚型TH1和TH2细胞，并且它们分泌的细胞因子和效应功能不同。TH1细胞主要分泌IFN-γ、IL-2、TNF-α和淋巴毒素（LT）等，介导细胞免疫，对胞内抗原产生免疫应答，与胞内病原体的清除和自身免疫疾病的诱发有关。TH2细胞主要分泌细胞因子IL-4、IL-5、IL-10和IL-13等，介导体液免疫。     

Calpain inhibitor I对烧伤小鼠肝脏NF-κB转录及炎性细胞因子分泌的影响

探讨Calpain inhibitorI（CI—I）对严重烧伤小鼠肝脏IκBα表达，NF-κB转录及炎性细胞因子分泌的影响。将CI-I腹腔给药预处理小鼠1h后背部行20％全身体表面积（TBsA）Ⅲ度烧伤，收集肝组织，检测其IκBα表达，NF-κB转录和血清TNF-α、IL-1β、IL-6分泌水平。与烧伤对照组比较，CI-I预处理后肝脏NF-κB转录活性和炎性细胞因子分泌有所降低。提示CI-I预处理可有效抑制严重烧伤小鼠肝细胞NF-κB活化和血清炎性细胞因子分泌，从而有利于烧伤后的炎症调节。     

供者特异性T细胞疫苗延长同种肝移植存活及其机制的初步分析

为检测细胞因子(CK)在肝移植物中的表达,探讨供者特异性T细胞疫苗(TCV)延长同种肝移植存活的机制。术前分别用特异和非特异TCV免疫受者,另设单纯移植对照。大鼠原位肝移植后观察肝移植物的存活时间(MST);术后第7天获取移植物,作组织切片观察;通过RT-PCR检测肝移植物内IL-2、IFN-γ、IL-4和IL-10的表达水平;进行混合淋巴细胞反应。结果发现供者特异性LCTCV组MST(15.7±4.2)d比非特异性LTCV组(11.3±2.7)d显著延长(P<0.01),而单纯移植组MST为(5.7±1.4)d(P<0.05);组织切片观察特异性LCTCV组未发现明显排斥改变;与其他两组比较,特异性LCTCV组MLR受到显著抑制(P<0.01);RT-PCR显示:特异性LCTCV组IL-4、IL-10的表达水平显著高于其他两组,IL-2和IFN-γ在单纯移植组呈高表达,同时IFN-γ在非特异LTCV组有表达。实验表明:细胞因子网络调控在免疫耐受形成中发挥重要作用,IFN-γ和IL-2主要参与急性排斥反应,IL-4和IL-10促进同种耐受的形成,不同的微环境下同一种细胞因子所发挥的主要作用会有所变化。     

sGVHD小鼠结肠IEL细胞CD137 和Th1细胞因子的表达

目的研究协同刺激分子CD137和Th1类细胞因子在小鼠同基因型移植物抗宿主疾病（sGVHD）中的作用。方法受体鼠用同基因型骨髓移植后,用环孢菌素A（CsA）诱导3周建立小鼠sGVHD模型;从小鼠结肠中分离上皮内淋巴细胞;用流式细胞术测定细胞亚群,RT-PCR方法检测CD137和Th1类细胞因子的表达,^3H掺入法测定T细胞增殖的抑制。结果sGVHD时,小鼠病变器官结肠上皮内淋巴细胞（IEL）中CD137及Th1类细胞因子（IL-12,IFN—γ,TNF-α）表达较正常,而移植对照组明显增高（P〈0．01）;IFN-γ的增高始于环胞霉素A诱导治疗后3周,而CDl37和IL-12、TNF-α表达增高仅在出现GVHD样症状时,Th2类细胞因子（IL-4、IL-10）在GVHD的诱导和发生中均无明显改变。     

体外阻断CD134对LN患者外周血单个核细胞TH1/TH2细胞因子表达的影响

目的 探讨CD134／CD134L共刺激分子对TH1，TH2细胞因子表达的影响及在狼疮性肾炎（LN）发病机制中的可能作用。方法活动期LN患者10例，分别采取外周静脉血，用密度梯度离心法制备新鲜PBMC，分成6组：（1）对照培养组；（2）单纯刺激组；（3）抗CD134组；（4）抗Ⅱ，4组；（5）rhCD134：Fc组；（6）地塞米松（Dex）组。另选取10例健康体检者作为健康对照组。采用ELISA法分别测定培养液上清中IFN-γ、IL-4、IL-10表达水平。结果（1）在抗CD3ε单抗／rIL-2刺激前，活动期LN患者PBMC培养液上清分泌的IFN-γ、IL-4和IL-10水平都明显高于健康对照组；（2）在抗CD3ε单抗／rIL-2刺激下，活动期LN患者PBMC分泌的IFN-γ，4和IL-10又较刺激前明显增加；（3）抗IL-4单抗、抗CDl34单抗均可使经抗CD3ε单抗／rIL-2刺激的LN患者PBMC分泌IL-4、IL-10水平显著下降，导致IFN-γ水平显著增高，免疫应答朝TH1方向偏离；（4）Dex能显著抑制抗CD3ε单抗／rIL-2刺激的原代培养PBMC中IL-4、IFN-γ的分泌水平，但对IL-10的产生并没有明显的抑制或促进作用；（5）rhCD134：Fc能显著降低抗CD3ε单抗／rIL-2刺激的原代培养PBMC中IFN-γ及IL-4、IL-10的分泌水平，对TH1和TH2细胞因子的产生都有显著抑制作用。结论糖皮质激素的抗炎机制具有多重性，对TH1、TH2细胞因子的作用并不均衡；抗CD134单抗对减轻LN患者PBMC的异常活化有一定作用；CD134-IgG融合蛋白与抗CD134单抗相比，抑制作用更明显，对急性期LN有更好的治疗作用。     

反义脱氧寡核苷酸静脉输注抑制小鼠MD-1表达延长皮肤移植物存活时间的研究

目的 静脉输注反义脱氧寡核苷酸（简称反义核酸,AS-ODN）抑制小鼠MD-1表达,并初步探讨MD-1用于排斥反应诊断的前景.方法 实验组（组1和组2）和阳性对照组（组3）行C57BL/6-BALB/c同种皮肤移植,阴性对照组（组4）行BALB/c-BALB/c同基因皮肤移植后,分别静脉输注小鼠MD-1 AS-ODN（组1）、随机序列脱氧寡核苷酸（组2）或生理盐水（组3和组4）.于术后第11天留样检测脾细胞MD-1表达水平（FACS）、脾细胞增殖反应强度（AlamarBlue还原率）、血清IL-2和IL-10水平（ELISA）以及皮肤移植物组织学改变（组织病理学检查）,并记录移植物存活时间.结果 静脉输注小鼠MD-1 AS-ODN能明显减少BALB/c小鼠脾细胞中MD-1阳性细胞百分数,降低脾细胞对特异性和非特异性刺激的增殖反应强度,下调血清IL-2水平和上调IL-10水平,减少移植物局部淋巴细胞浸润,并显著延长同种皮肤移植物存活时间.结论 静脉输注MD-1 AS-ODN特异性抑制小鼠MD-1表达可显著延长皮肤移植物的存活时间.MD-1表达水平对排斥反应的发生具有一定的指示作用.     

Schizophrenia in a North Swedish geographical isolate, 1900–1977. Epidemiology, genetics and biochemistry

Over 200 schizophrenic patients belonging to three major and interrelated pedigree complexes have been investigated over the past 30 years in a North Swedish geographically isolated population, presently numbering about 6,000. An intensive investigation of a number of biochemical correlates and genetic markers in a few selected families belonging to one of the major pedigrees has indicated new strategies for the current research program.
Schizophrenia, as defined operationally, is significantly associated with decreased activities of two enzymes (1) blood platelet monoamine oxidase, (2) plasma dopamine-β-hydroxylase, and (3) with the genetic marker Gc² (group specific antigen). Both enzymes are subject to genetic variation. A positive score for linkage between schizophrenia and low plasma DBH activity has been calculated, but, so far, available data are insufficient for discrimination between linkage and partial contribution of genetically controlled low plasma DBH to the pathogenesis of the disease. Alternatively, both mechanisms could be involved.
As a model for continued research, schizophrenia is explained as based on a double dominant-recessive genotype (Aabb), representing a vulnerability which in about 50 % of cases develops into clinical schizophrenia. It is suggested that the dominant mutation (A) operates on or affects MAO activity, and that the recessive genotype (bb) is instrumental in low variates of DBH activity and very likely such variates within the normal range of physiological variation. Moreover, it is suggested that the combined effects of MAO- and DBH-reduced efficiency on the metabolism of e.g. dopamine could be an essential pathogenic mechanism for the schizophrenic illness which is segregating in this population.     

The dominant diseases of modernized societies as omega-3 essential fatty acid deficiency syndrome: Substrate beriberi

About 1900, modern food selection and processing caused widespread $\text{epidemics}$ of the B vitamin deficiency diseases of beriberi and pellagra which, for genetic reasons, often expressed as different diseases ranging from bowel and heart disease to dermatoses and psychoses. But the B vitamins merely help convert essential fatty acids (EFA) into the prostaglandin (PG) tissue regulators and it now turns out that, through hydrogenation, milling and selection of w3-poor southern foods, we have also been systematically depleting, by as much as 90%, a newly discovered trace Nordic EFA (w3) of special importance to primates and sole precursor of the PG3(4) series, even as a concurrent fiber deficiency increases body demand for EFA. Since substrate EFA is processed by many B vitamin catalysts, an EFA deficiency will mimic a $\text{panh}$ypovitaminosis B, i.e., a mixture of $\text{substrate}$ beriberi and $\text{substrate}$ pellagra resembling vitamin beriberi and pellagra but exhibiting as even more diverse $\text{endemic}$ disease. This would consitute a second stage of the Modern Malnutrition and explain why some workers now hold the dominant diseases of modermized societies to be new, nutritionally based, pellagraform yet lipid-related and to range, once again, from heart disease to psychosis. It is an assumption that our dominant diseases are unrelated to each other or are merely revealed by our diagnostic acumen and therapeutic success; and that hydrogenating millions of tons of food oils annually, to destroy the rancidity producing w3-EFA, is safe for $\text{primates}$. Extensive beriberiform disease is reported here in 32 typical cases taken from medical practice which responds strikingly to linseed oil supplements (60% w3-EFA) in confirmation of identical results in Capuchins.     

The universal muscular chain reaction,muscle spasm,Torsions, ruptures and extravasations. Chameleons of pathology and some manifestations of simple muscular disorders

Most bodily functions require the coordinated actions of complementary and supplementary paired muscle groups. Where this essential muscular cooperation is lacking, hollow organs may burst and others become literally screwed up, giving rise to many similar spastic diseases such as Torticollis, Twisted ovarian cyst, Torsion of the Testis, Volvulus of the intestines, Varicose Veins, Megacolon, Aortamegaly, Scoliosis, Erb's Palsy, Peyronie's Disease, Main-en-Griffe, Undescended Foot (Pes Cavus), Talipes, Strabismus. Spasm is “panenepidemic” and unclassified examples of Torsion Dystonia and Dyskinesia really are as common as debt and taxes.     

'Very sore nights and days': the child's experience of illness in early modern England, c.1580-1720

Sick children were ubiquitous in early modern England, and yet they have received very little attention from historians. Taking the elusive perspective of the child, this article explores the physical, emotional, and spiritual experience of illness in England between approximately 1580 and 1720. What was it like being ill and suffering pain? How did the young respond emotionally to the anticipation of death? It is argued that children’s experiences were characterised by profound ambivalence: illness could be terrifying and distressing, but also a source of emotional and spiritual fulfilment and joy. This interpretation challenges the common assumption amongst medical historians that the experiences of early modern patients were utterly miserable. It also sheds light on children’s emotional feelings for their parents, a subject often overlooked in the historiography of childhood. The primary sources used in this article include diaries, autobiographies, letters, the biographies of pious children, printed possession cases, doctors’ casebooks, and theological treatises concerning the afterlife.     

Guidelines for the Validation and Use of Immunoassays for Determination of Introduced Proteins in Biotechnology Enhanced Crops and Derived Food Ingredients

Recent advancements in agricultural biotechnology have created a need for analytical techniques to determine introduced proteins in crops enhanced through modern biotechnology techniques. These proteins are expressed in plant tissues and may be present in food ingredients. Immunoassays are ideally suited for protein detection and may be used as both quantitative and threshold methods. Microplate ELISA and lateral flow devices are two of the most commonly used immunoassay formats for agricultural biotechnology applications. This paper provides general background information and a discussion of criteria for the validation and application of immunochemical methods to the analysis of proteins introduced into plants and food ingredients using biotechnology methods. It is the result of a collaborative effort of members of the Analytical Environmental Immunochemical Consortium. This collaborative effort represents the combined expertise of several organizations to reach consensus on establishing guidelines for the validation and use of immunoassays. Further, the paper offers developers and users a consistent approach to adopting the technology as well as aid in producing accurate and meaningful results.     

Ultracryotomy: development and application (with examples from the yeast cytology) (author's transl)

The preparation steps usually necessary for obtaining ultrathin frozen sections of biological material (chemical prefixation, enclosing, cryoprotective treatment, freezing, sectioning, and post-staining the sections for transmission electron microscopy) are submitted to a critical analysis. The application of cryo-ultramicrotomy, in particularly for cytochemical purposes, is reviewed. Fundamental considerations of chemical prefixation and poststaining are supported by examples from yeast cytology. Furthermore, the efficiency of the cryo-ultramicrotomy (electron optical resolution of ultrastructural details) is demonstrated on yeast cells and protoplasts.     

Hypo- und Hypermagnesämie aus kardiologischer Sicht

Zusammenfassung Eine Reihe pathologischer Zustände bedingen Magnesiummangel. Zustände mit Hypermagnesämie sind ebenfalls bekannt, doch wesentlich seltener. Für den Kardiologen beachtenswert ist, daß unter Therapie mit bestimmten Diuretica bei Herzinsuffizienz, bei Herzinfarkt, Kardiomyopathie, Digitalisintoxikation und bestimmten Herzrhythmusstörungen Hypomagnesämie beobachtet wurde. Leider kann in der klinischen Routine nur ein extracelluläres Magnesiumdefizit durch Serumbestimmungen gemessen werden; über Magnesiummangel einzelner Organe kann nichts ausgesagt werden. Hinweise für Magnesiummangel geben aber neben der Messung des Serumspiegels Anamnese, klinischer Befund, bestimmte EKG-Veränderungen wie auch evtl. Hypokalämie, ein Zustand, bei dem sich oft — besonders bei Aldosteronismus — parallele Veränderungen zeigten.Tierexperimente deuten darauf hin, daß infarktähnliche Läsionen unter Magnesiummangel entstehen, doch ob Herzinfarkt beim Menschen durch Magnesiummangel ausgelöst werden kann, ist noch ungeklärt. In Leichenherzen zeigte sich im Infarktgebiet neben Calciumakkumulation signifikanter Magnesiumverlust, wobei unklar blieb, ob sich Ursache oder Folge des Infarktes widerspiegelten. Falls ein ursächlicher Zusammenhang besteht, ist er im Myokardstoffwechsel selbst zu suchen, wie bei der Alkoholkardiomyopathie, wo myokardialer Magnesiummangel zumindest als pathogenetischer Teilfaktor anerkannt wird. Andererseits versucht man aber auch Beziehungen zwischen Atherosklerose, Blutgerinnung und Hypomagnesämie herzustellen, in der Meinung, daß Magnesiummangel auch über den coronaren Pathomechanismus des Herzinfarktes wirken könnte. Sicher scheint, daß gewisse EKG-Veränderungen und Herzrhythmusstörungen durch einen irritierten Magnesiumhaushalt bedingt sein können, da sie bei Gabe bzw. Entzug von Magnesium verschwinden. Daß Magnesiummangel die Glykosidtoleranz verringert, wird tierexperimentell bestätigt. Unter Hypomagnesämie bewirkt Acetylstrophanthidin eher und länger Rhythmusstörungen als ohne, außerdem lassen diese sich durch Magnesiumgaben eliminieren. Da in gewissen Fällen spontane und digitalisinduzierte Herzrythmusstörungen durch Magnesiuminjektionen beseitigt wurden, scheint Magnesium als Therapeuticum angebracht. Einsatz verschiedener Magnesiumsalze bei Angina pectoris, degenerativen Herzerkrankungen und Herzinsuffizienz ohne geprüften und offensichtlich gestörten Magnesiumhaushalt ist fragwürdig, weil keine eindeutigen klinischen Erfolgsbeweise vorliegen. Immerhin mag es aber larvierte, durch Serumbestimmungen nicht erfaßbare Mangelzustände geben. Allgemein erscheint es aus kardiologischer Sicht ratsam, den Magnesiumhaushalt zu überwachen und in entsprechenden Fällen auszugleichen, um möglichen Myokardläsionen oder fatalen Herzrhythmusstörungen entgegenzuwirken.     

HLA in North Colombia Chimila Amerindians

HLA-A,-B,-C,-DRB1 and -DQB1 alleles have been studied in Chimila Amerindians from Sabana de San Angel (North Colombian Coast) by using high resolution molecular typing. A frequent extended haplotype was found:HLA-A*24:02-B*51:10-C*15:02-BRB1*04:07-DQB1*03:02 (28.7%) which has also been described in Amerinndian Mayos Mexican population (Mexico, California Gulf, Pacific Ocean). Other haplotypes had already been found in Amerindians from Mexico (Pacific and Atlantic Coast), Peru (highlands and Amazon Basin), Bolivia and North USA. A geographic pattern according to HLA allele or haplotype frequencies is lacking in Amerindians, as already known. Also, five new extended haplotypes were found in Chimila Amerindians. Their HLA-A*24:02 high frequencies characteristic is shared with aboriginal populations of Taiwan; also, HLA-C*01:02 high frequencies are found in New Zealand Maoris, New Caledonians and Kimberly Aborigines from Australia. Finally, this study may show a model of evolutionary factors acting and rising one HLA allele frequency (-A*24:02), but not in others that belong to the same or different HLA loci.     

The case for allele‐specific recognition by the TCR

There is a sharp difference in how one views TCR structure–function–behaviour dependent on whether its recognition of major histocompatibility complex‐encoded restriction elements (R) is germline selected or somatically generated. The generally accepted or Standard model is built on the assumption that recognition of R is by the V regions of the αβ TCR, which is not driven by allele specificity, whereas the competing model posits that recognition of R is allele‐specific. The establishing of allele‐specific recognition of R by the TCR would rule out the Standard model and clear the road to a consideration of a competing construct, the Tritope model. Here, the case for allele‐specific recognition (germline selected) is detailed making it obvious that the Standard model is untenable.