HLA & Immunogenetics Frequently Asked Questions

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  1. What is HLA?
  1. HLA stands for Human Leukocyte Antigen. It is the name given to the Major Histocompatibility Complex (MHC) of man.

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  1. What is HLA typing and why is it done?
  1. The HLA complex of genes on human chromosome 6 encodes proteins that are centrally involved in the actions of the immune system. In response to the diversity of infectious agents that have threatened human populations, the HLA genes have themselves diversified to the point at which most individuals have a different HLA type.

    These genetic differences individualize a person's immune system. The combination of class I and class II antigens expressed by a person is called his/her HLA phenotype. The combination of class I and class II alleles is the HLA genotype. In most cases, the genotype reflects the phenotype.

    HLA typing identifies a person's HLA type and, therefore, helps to characterize the immune function of that person. Different loci and different levels of resolution are required for different clinical applications.

    HLA typing is routinely used for matching donors and recipients in solid organ or hematopoietic stem cell transplantation (HSCT) / bone marrow transplantation, for helping in the diagnosis of certain autoimmune or anti-inflammatory diseases, and for determining eligibility of patients to tumor vaccination protocols when the vaccine is HLA-allele dependent.

    A major area of development in HLA is vaccination and immunotherapy clinical trials and epitope discovery for infectious diseases and cancer.

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  1. Which HLA typing tests should I order for kidney transplantation?
  1. Tests for screening solid organ transplant recipient and potential donor(s) prior to enrollment in a transplant registry include:
    • HLA Class I A, B, C DNA Typing (15484X)
    • HLA Class II DR, DQ DNA Typing (15485X)

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  1. Which HLA typing tests should I order for Bone Marrow Transplantation?
  1. Tests for initial HLA screening for transplant recipient and genetically related potential donor(s) include:
    • HLA Class I A, B, C DNA Typing (15484X)
    • HLA Class II DR, DQ DNA Typing (15485X)
    Tests to determine HLA type of transplant recipient and unrelated potential donor(s) or to perform second-level testing for determining HLA type in transplant recipient and genetically related potential donor(s) include:
    • HLA-A High Resolution SBT Typing (17397X)
    • HLA-B High Resolution SBT Typing (17396X)
    • HLA-C High Resolution SBT Typing (17395X)
    • HLA-DRB1 High Resolution SBT Typing (17393X)
    • HLA-DQB1 High Resolution SBT Typing (17394X)
    • HLA-A2 Typing with Reflex to A2 High Resolution SBT Sub typing (17398X)

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  1. What HLA typing test should I order for platelet refractoriness?
  1. Tests to identify HLA-compatible platelets to improve platelet survival after transfusion includes: HLA-A, B Class I DNA Typing (15757X). Platelet cross-matching and STAT services are not provided.

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  1. Which test should I order for A29?
  1. HLA-A Class I DNA typing (test code 10951X).

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  1. Which test should I order for B5?
  1. HLA-B Class I DNA typing (test code 10950X).

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  1. Which test should I order for DR4?
  1. HLA-DRB1 Class II DNA typing (test code10952X).

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  1. What are the serological name equivalents for HLA-A, B, C, DRB1 and DQB1 alleles?
  1. The following tables list the serological equivalents used by our Immunogenetics Department when reporting results obtained for low/intermediate resolution HLA genotyping. The nomenclature chosen follows the WHO nomenclature report (Marsh, et al.) and the HLA dictionary (Schreuder, et al.).

    2. HLA-A

    Serological Name

    Alleles

     

    Broad Specificity

     

    A1

    -

    A*01

    A2

    -

    A*02

    A3

    -

    A*03

    A11

    -

    A*11

    A23

    A9

    A*23

    A24

    A9

    A*24

    A25

    A10

    A*25

    A26

    A10

    A*26

    A29

    A19

    A*29

    A30

    A19

    A*30

    A31

    A19

    A*31

    A32

    A19

    A*32

    A33

    A19

    A*33

    A34

    A10

    A*34

    A36

    -

    A*36

    A43

    -

    A*43

    A66

    A10

    A*66

    A68

    A28

    A*68

    A69

    A28

    A*69

    A74

    A19

    A*74

    A80

    -

    A*80

    HLA-B

    Serological Name

    Alleles

     

    Broad Specificity

     

    B7

    -

    B*07

    B8

    -

    B*08

    B13

    -

    B*13

    B64

    B14

    B*1401

    B65

    B14

    B*1402

    B62

    B15

    B*1501, 04, 05, 06, 07, 15, 20, 24,
    25, 27, 30 32, 35, 39, 45, 48, 58

    B63

    B15

    B*1516, 17,

    -

    B70

    B*1509, 37, 51,

    B71

    B70

    B*1510, 18

    B72

    B70

    B*1503, 46,

    B75

    B15

    B*1502, 08, 11, 21, 31,

    B76

    B15

    B*1512, 14, 19,

    B77

    B15

    B*1513

    B35

    -

    B*1522, 59,

    B18

    -

    B*18

    B27

    -

    B*27

    B35

    -

    B*35

    B37

    -

    B*37

    B38

    B16

    B*38

    B39

    B16

    B*39

    B60

    B40

    B*4001, 07, 10, 31, 34,

    B61

    B40

    B*4002, 03, 04, 06, 09, 16, 27, 29,

    B41

    -

    B*41

    B42

    -

    B*42

    B44

    B12

    B*44

    B45

    B12

    B*45

    B46

    -

    B*46

    B47

    -

    B*47

    B48

    -

    B*48

    B49

    B21

    B*49

    B50

    B21

    B*50

    B51

    B5

    B*51

    B52

    B5

    B*52

    B53

    -

    B*53

    B54

    B22

    B*54

    B55

    B22

    B*55

    B56

    B22

    B*56

    B57

    B17

    B*57

    B58

    B17

    B*58

    B59

    -

    B*59

    B67

    -

    B*67

    B73

    -

    B*73

    B78

    -

    B*78

    B81

    -

    B*81

    -

    -

    B*82

    -

    -

    B*8301

    HLA-C

    Serological Name

    Alleles

     

    Broad Specificity

     

    C1

    -

    C*01

    C2

    -

    C*02

    C3

    -

    C*03

    C4

    -

    C*04

    C5

    -

    C*05

    C6

    -

    C*06

    C7

    -

    C*07

    -

    -

    C*08

    -

    -

    C*12

    -

    -

    C*13

    -

    -

    C*14

    -

    -

    C*15

    -

    -

    C*16

    -

    -

    C*17

    -

    -

    C*18

    HLA-DRB1

    Serological Name

    Alleles

    DR51, 52, 53 Linkage

     

    Broad Specificity

     

     

    DR1

    -

    DRB1*01

    -

    DR17

    DR3

    DRB1*0301, 04, 05, 10, 11

    DR52 (DRB3*)

    DR18

    DR3

    DRB1*0302, 03

    DR52 (DRB3*)

    DR4

    -

    DRB1*04

    DR53 (DRB4*)

    DR7

    -

    DRB1*07

    DR53 (DRB4*)

    DR8

    -

    DRB1*08

    -

    DR9

    -

    DRB1*0901

    DR53 (DRB4*)

    DR10

    -

    DRB1*1001

    -

    DR11

    DR5

    DRB1*11

    DR52 (DRB3*)

    DR12

    DR5

    DRB1*12

    DR52 (DRB3*)

    DR13

    DR6

    DRB1*13

    DR52 (DRB3*)

    DR14

    DR6

    DRB1*14

    DR52 (DRB3*)

    DR15

    DR2

    DRB1*15

    DR51 (DRB5*)

    DR16

    DR2

    DRB1*16

    DR51 (DRB5*)

    HLA-DQB1

    Serological Name

    Alleles

     

    Broad Specificity

     

    DQ2

    -

    DQB1*02

    DQ7

    DQ3

    DQB1*0301, 04

    DQ8

    DQ3

    DQB1*0302, 05

    DQ9

    DQ3

    DQB1*0303

    DQ4

    -

    DQB1*04

    DQ5

    DQ1

    DQB1*05

    DQ6

    DQ1

    DQB1*06

    References

    Marsh SGE, et al. Nomenclature for factors of the HLA system, 2002. Tissue Antigens. 2002;60:407-464.

    Schreuder GM et al. The HLA Dictionary 2001: a summary of HLA-A, -B, -C, -DRB1/3/4/5 and -DQB1 alleles and their association with serologically defined HLA-A, -B, -C, -DR and -DQ antigens. Eur J Immunogenet. 2001;28:565-596.

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  1. What does "class I" or "class II" in the test name signify?
  1. The Class I region of the HLA complex includes, among other genes, HLA-A, -B, and -C. These loci code for the heavy chain of the MHC class I molecules expressed on most cells.

    The Class II region includes, among other genes, the HLA-DRBA1, -DQA1 and -DPA1genes, which code for the alpha chains of the DR, DQ and DP class II molecules. HLA-DRB1, -DQB1 and -DPB1 code for the beta chain of the DR, DQ and DP class II molecules. In addition to HLA-DRB1, which codes for the primary HLA specificities such as DR1, DR2, DR4, etc., other DRB genes code for the beta chain of the specificities DR52 (DRB3), DR53 (DRB4), and DR51 (DRB5), not present in all haplotypes.

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  1. See larger version

    What does the map of the HLA region look like?
  1. The segment of the small arm of chromosome 6 that contains the HLA complex is shown in detail in the HLA map to the right (click the image to see a larger version). The first bar shows the division of the complex into class I, II, and III regions. The ruler indicates number of kilobases. The gene map shows the approximate positions of the gene loci mentioned in the text. Bars to the right show expressed genes and to the left, pseudogenes (not expressed). In bold are shown the genes coding for the heavy chain of the classical class I molecules and the alpha and beta chains of the class II molecules.

    Class I region: HLA-A, -B, and -C code for the heavy chain of the MHC class I molecules expressed on most cells. HLA-F, -G and -E code for the heavy chain of non-classical class I genes, with highly specialized functions. The MIC genes or human MHC class I chain-related genes encode stress inducible proteins, implicated in the regulation of NK cell activity.

    HFE is a class I-like gene located approximately 4 Mb telomeric of HLA-F. It is responsible for the disease hereditary hemochromatosis.

    Class II region: The HLA-DRBA1, -DQA1 and -DPA1 genes code for the alpha chains of the DR, DQ and DP class II molecules. HLA-DRB1, -DQB1 and -DPB1 code for the beta chain of the DR, DQ and DP class II molecules. In addition to HLA-DRB1, which codes for the primary HLA specificities such as DR1, DR2, DR4, etc., other DRB genes code for the beta chain of the specificities DR52 (DRB3), DR53 (DRB4), and DR51 (DRB5), not present in all haplotypes. The DO and DM molecules regulate the loading of exogenous peptides into class II molecules. LMP2 and LMP7, which encode subunits of the proteasome, and TAP1 and TAP2, which encode a peptide transporter, are involved in the processing and presentation of antigens by class I molecules.

    Class III region: TNFB and A code for tumor necrosis factors; HSP genes for heat shock proteins; C2, Bf, and C4 genes for proteins of the complement system; and P450-C21B for a steroid 21-hydroxylase.

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  1. What are the diseases associated with HLA?
  1. HLA molecules play a central role in the immune response. They are so polymorphic that the HLA type individualizes a person's immune response and, therefore, is associated with the person's susceptibility to several autoimmune and auto-inflammatory diseases. These diseases are usually polygenic and triggered or influenced by environmental factors; therefore, a person's HLA type is only one component of his/her susceptibility towards the disease. Some of the most common associations are listed below:

    HLA-B27

    Ankylosing spondylitis, acute anterior uveitis

    HLA-DQ2, 8

    Celiac disease

    HLA-DR15, DQ6

    Narcolepsy

    HLA-DR3, 4

    Diabetes

    HLA-DR4

    Rheumatoid arthritis

    Certain HLA-disease associations are commonly used for diagnosis. We have established specific test codes for them and indicate the diagnostic use in the test name. We perform the same tests as those listed for intermediate resolution typing, but the physician does not need to specify the locus or allele when ordering. Additionally, we provide a brief comment on the clinical significance of the test.

    Test

    Test Code

    Loci Tested

    Clinical Application

    HLA Typing for Celiac Disease

    17135X

    HLA‑DQB1

    Susceptibility to celiac disease.HLA-DQ2 and DQ8 are the variants associated.

    HLA Typing for Narcolepsy

    34399Z

    HLA‑DRB1 and DQB1

    Susceptibility to narcolepsy and other neurological disorders.HLA-DR15 and HLA-DQ6 are the variants associated.

    HLA-B27 DNA Typing

    15584Z

    HLA‑B

    Susceptibility to ankylosing spondylitis and other arthropaties.As the title of the test indicates, HLA-B27 is the variant associated.

    To use HLA typing for diagnosis of other disorders, physicians can specify an HLA variant, eg, HLA-DR4. The test to be ordered is the locus of which that variant is a part, eg, in the case of HLA-DR4, order HLA-DRB1 Class II DNA typing, test code 10952X.

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