I. Introduction
• Major histocompatibility antigen system
• Major histocompatibility complex:
– A large genetic locus that includes
the highly polymorphic genes
encoding the peptide-binding
molecules recognized by T
lymphocytes. The MHC locus also
includes genes encoding cytokines,
molecules involved in antigen
processing, and complement proteins.
• H-2 complex: murine MHCs
• HLA: human MHC which is known as the human
leucocytes antigen system.
– Three classes of MHC genes closely
linked on chromosome
• ClassⅠgene
• ClassⅡgene
• ClassⅢgene
II. The organization of murine and
human MHC
1. Mouse H-2 complex:
– ClassⅠgene: K, DL class
Ⅰmolecules (αchain）
– ClassⅡgene: I class
Ⅱmolecules (αβchain)
– ClassⅢgene: S complement,
TNF
SK I D/L
Chr. 17centromer
e
H-2
2. Human HLA complex:
DP DN DO DQ DR B C E A
G
HLA
comple
x
centromere Chr. 6
class loci Proteins encoding
HLA class Ⅰ Classical B, C, A HLA class Ⅰmolecules
Non-classical E, F, G
HLA classⅡ Classical DP, DQ, DR HLA class IⅠmolecules
Non-classical DN, DO
HLA class Ⅲ Complement, TNF, HSP
V. Genetics of MHC
• Polygenic
• Polymorphic
• Haplotype inherited
• Codominant
A. HLA-Ⅰmolecules
III. The structure and function of
MHC molecules
1. Structure
– Two polypeptide chain: H-chain
and β2-microglobulin (not coded by the
MHC)
– Heavy chain has 3
domains:α1,α2,α3.
– Heavy chain α1andα2 domains
form the binding groove (the
polymorphic region)
– α3 domain bind to CD8
2. Cellular distibution
– ClassⅠ molecules are expressed
on all nucleated cells (all cells
except for RBC )
• Exists in the form of
– Membrane bound molecules
– Soluble molecules
2. Function
i. Antigen processing and
presenting (endogeneous
pathway)
– peptides generated in the cytosol (eg.
Virus antigen) become associated
with MHC class Ⅰmolecules which
move to the surface and can be
recognized by CD8+ T cell (cytotoxic
T lymphocytes) .
ii. Involve in transplant rejection
cell development in thymus
B. HLA-Ⅱmolecules
1. Structure
– Heterodimers of α
andβglycoprotein chains.
– Each chain has 2domains(α1, α2
and β1, β2)
– α1 and β1 form the binding
groove. (the polymorphic region)
– CD4 bind to β2 domain
2. Cellular distribution
– class Ⅱmolecules are expressed
on
• B cells
• Mφ
• Dendritic cells
• Vascular endothelial cells
3. Functions
i. Antigen processing and presenting
(exogeneous pathway):
– both pathogens in cellular vesicles and
those come from outside the cell are
presented on MHC class Ⅱmolecules
of APCs and are transported to the cell
surface where they can be recognized
by CD4 + T cell
ii. Involve in transplant rejection
of immune response
iv. T cell development in the thymus
C. Non-classical HLA
– (HLA-Ⅰb)
1. Differentiation or activation states
2. Disease
3. Cytokines
IV. Factors influencing the expression
of HLA molecules
（（11）内源性抗原提呈：抗原）内源性抗原提呈：抗原 靶细胞靶细胞
组成组成HLAⅠHLAⅠ类分子类分子--抗原肽复合物抗原肽复合物 表达于细表达于细
胞膜表面胞膜表面 CD8+TCD8+T细胞识别。细胞识别。
（（22）外源性抗原提呈：）外源性抗原提呈：抗原抗原 APC APC
HLAⅡHLAⅡ类分子类分子--抗原肽复合物抗原肽复合物 表达于细胞表达于细胞
膜表面膜表面 CD4+TCD4+T细胞识别细胞识别。。
HLA与疾病的关系
（一） (relative risk，相对危险率)
值越大相关性越强。
（二）举例
1.强直性脊柱炎与B27
2.胰岛素依赖性糖尿病（IDDM）与DR3、DR4
病人（病人（Ag+/Ag-Ag+/Ag-））
对照（对照（Ag+/Ag-Ag+/Ag-））
＝
VI. Significance of MHC
1. Control of immune response
• MHC restriction:
– The ability of T lymphocytes to respond
only when they are presented with the
appropriate antigen in association with
either “self” MHC class Ⅰor
classⅡmolecules.
• Ir gene (immune response gene)
血清学 细胞学 分子生物学
实验方法 补体介导的微
量细胞毒试验
混合淋巴细
胞培养法
（MLC)
分子生物学
技术
原理 抗体(HLA分型)
+ 淋巴细胞(受
者) + 补体淋
巴细胞受损
判定结果（细
胞死亡百分率）
单向法
双向法
比较供、受
者编码HLA
抗原基因的
DNA序列，
判定供、受
者间的相似
程度。
主要应用 检测HLA-A、B
、C抗原
检测DR抗原
HLA分型法原理及应用
2. Graft rejection and tissue
matching
3. Autoimmune disease
susceptibility
Summury
