International Cell Exchange

• History
• Contributions to HLA
• Publications
• HLA Dictionary
• Worldwide Participation
• Program Information
• Report Nomenclature

History

The UCLA International Cell Exchange has followed the progress in HLA typing since it began with 85 participating laboratories in 1974 and has expanded to 200 participants worldwide . The original goal of the Cell Exchange was to standardize the practice of HLA typing. This was an important undertaking because tissue typing for organ transplantation, disease studies, and population studies was dependent upon human typing sera obtained in very limited quantities, primarily from multiparous women. The accuracy of these reagents was dependent upon local methods of assessing the specificities of the anti-HLA antibodies and the volumes made it difficult to distribute sufficient quantities for use by everyone who performed HLA testing.

The Cell Exchange provided an alternative strategy, distributing the same cells to many laboratories for HLA typing. Each laboratory would report their results to UCLA and then receive a report of every other laboratory's results for comparison. This provided the laboratories a means for evaluating their typing results and for identifying the weaknesses in their panels of typing sera. As the complexity of the HLA system defined by antibody reagents grew, the Cell Exchange focused its efforts on providing challenging cell types - those that included "rare" HLA antigens or unusual combinations of antigens that might be difficult to discriminate.

A serum exchange was added in 1981, to check for anti-HLA antibody specificities. Accuracy of specificity and degree of sensitivity by various methods are assessed. Sera with complexes, interlocus antibodies, and reagent-quality antibodies are examined. This exchange helps labs detect problems in their serum screening panels and procedures.  In 1987, testing for Class II typing was initiated with the first shipment of 2 lymphoblastoid cell lines. In 1990, DNA-based typing results were first reported in correlation with the serologic results. Cells with rare alleles and unusual DR-DQ associations are studied. DRB1, DRB3, DRB4, DRB5, DQB1, DQA1, and DPB1 alleles are evaluated. These cell lines can be maintained in culture and used as reference lines.

In 1994, the Cell Exchange initiated offering the same cells for molecular typing as for serologic typing for Class I. The data from the parallel typings is instrumental in identifying serologic equivalents for Class I and Class II alleles that previously had little or no serologic information. This information is routinely added to the HLA Dictionary.  In 1997, DNA extracts from cells with unusual class I alleles were provided to participating laboratories. Many of these extracts were from the reference cells sequenced for rare alleles, thus giving laboratories the opportunity to type them, whereas they may not detect them in routine typing them in their local populations. Having these cells typed by numerous laboratories will help to achieve standardization in the typing of rare types.

In 2005, the International KIR Exchange was integrated within the framework of the International Cell Exchange, by offering reference DNA samples for KIR gene typing. The goals of this program are to standardize typing of KIR genes and alleles, and to identify new alleles.

In February 2007, a pilot study for MICA (class I chain-related molecule A) typing was initiated by sending samples to a select number of laboratories. This will provide an opportunity to compare typing results from different technologies. In the near future, this will expand to encompass MICA antibody identification. The goals are to standardize typing of MICA alleles and MICA antibody identification, as well as to identify new alleles.

In all the exchanges, the goals are to provide samples to validate methods and reagents, and to provide external quality control. By offering a forum for data exchange and discussion, the Cell Exchange has played a key role in international standardization. The UCLA International Cell Exchange has recorded the progress of HLA typing in a number of publications and presentations at national and international meetings.

Contributions to HLA

The Cell Exchange has helped laboratories to sharpen their skills and has monitored and published the development of tissue typing over the years. The goal of providing unusual types or combinations to participants was often accomplished by identifying cells that gave ambiguous or incomplete results. Many of these cells were provided to the Cell Exchange by the participating laboratories and often these challenging HLA types were found to include "variants," which represented new alleles that were not defined by serology.

The problem of how to ship viable lymphocytes to locations throughout the world was solved by Dr Min Sik Park in 1973 (Park MS and Terasaki PI, Transplantation (1974) 18, 520-524) and permitted the evolution of international testing. This simple method is still used today by organizations involved in proficiency testing as well as for routine exchanges of material among laboratories.

Over the years, the Cell Exchange has helped to identify numerous new or rare antigens. In the course of standardizing specificities to attain international agreement, the exchanges have identified duplicate names for the same specificity and the same name being used for different ones, for example, A26 versus A66 for the antigen encoded by A*6601, and A34 versus A66 for the one encoded by A*6602.

More than 30 cells typed in the Cell Exchange now serve as reference cells for Class I alleles, confirmed through subsequent study. Examples of variants which were extensively studied in previous cell exchanges and received formal designations by the WHO Nomenclature Committee are: A9.3 (A*2403), BN21 (B*4005), B5.35 (B*5102), 5Y/8w58/BSNA (B*7801, B*7802), numerous B15 variants (B*1508, B*1511, B*1512, B*1515), and DT (B*8101). The Cell Exchange data has provided vital correlation between alleles and serologic names in many cases, such as establishing B*1518 as B71 and Cw*1701 as a short Cw7. Among the numerous alleles detected in exchange cells were A*1104, A*6803, B*1304, and B*4012. Our Cell Exchange continues to study serological variants not yet recognized and bring them to the forefront for validation by sequence analysis.

By routinely contributing data to be used in the HLA Dictionary that offers allele-serologic equivalents, the Cell Exchange provides valuable information to be used in matching searches for unrelated donors in databases with mixtures of data attained using different techniques. This is important during the transition period as labs migrate to the exclusive use of molecular testing methods.

The International Cell Exchange has a long and consistent history of service to the histocompatibility community. The Cell Exchange has operated continuously for more than thirty years, sending cells and sera, accounting for more than 3000 reference samples. The close of 2006 will mark the completion of 322 cell exchanges, encompassing 1288 cells for Class I serology, 920 sera for anti-HLA antibody identification, 386 cells for Class II serology, 310 cells for Class II DNA typing, and 464 cells for Class I DNA typing. The exchange has also provided 376 DNA extracts for HLA Class I testing.

Publications

1. Bernoco D, Perdue S, Terasaki Pi, Loon J, Park MS: International cell exchange. Transplant Proc 1978; 10:717.
2. Loon J, Takemura S, Terasaki PI: Ten-year progress report of the International Cell Exchange. Tissue Antigens 1984; 24:215.
3. Loon J, Terasaki Pi, Takemura S, Park MS: Standardization of HLA through an international calf exchange. In: Terasaki PI Ed. Clinical Transplants 1987. UCLA Tissue Typing Laboratory, Los Angeles, 1987; 453.
4. Lau M, Terasaki PI, Park MS, Barbetti A: Fifteen-year overview of the International Cell Exchange. In: Terasaki PI, Ed, Clinical Transplants 1989, p.447-456, 1989.
5. Lau M, Terasaki PI, Park MS, Barbetti A: 1990 Cell Typings in the International Cell Exchange. In: Terasaki PI, Ed, Clinical Transplants 1990, p.567-576.
6. Lau M, Terasaki PI, Park MS, Barbetti A: International Cell Exchange, 1991. In: Terasaki PI, Cecka JM, Eds, Clinical Transplant 1991, Los Angeles, UCLA Tissue Typing Laboratory, 1991; p.385-400.
7. Lau M, Terasaki PI, Park MS: International Cell Exchange, 1992. In: Terasaki PI, Cecka JM, Eds, Clinical Transplants 1992. Los Angeles, UCLA Tissue Typing Laboratory, 1992;457-473.
8. Lau M, Terasaki PI, Park MS: The 1993 Cell Typings of the International Cell Exchange. In: Terasaki PI, Cecka JM, Eds, Clinical Transplants 1993. Los Angeles, UCLA Tissue Typing Laboratory, 1993;533-552.
9. Lau M, Terasaki PI, Park MS: International Cell Exchange, 1994. In: Terasaki PI, Cecka JM, Eds, Clinical Transplants 1994. Los Angeles, UCLA Tissue Typing Laboratory, 1994;467-488.
10. Park MS, Lau M, Geer L, Terasaki PI: International Sera Exchange Analyses in Relation of DNA Sequences: Summary Report from 1990 to 1994. In: Terasaki PI, Cecka JM, Eds, Clinical Transplants 1994. Los Angeles, UCLA Tissue Typing Laboratory, 1994;489-508.
11. Lau M, Park MS, Terasaki PI: International Cell Exchange 1974-1996, a 23-year documentation. In: Terasaki PI and Gjertson DW, Eds. HLA 1997. Los Angeles, UCLA Tissue Typing Laboratory, 1997:85-124.
12. Lau M, Park MS, and Terasaki PI: 1997 Cell Typings in the International Cell Exchange. In: Gjertson DW, Terasaki PI Eds. HLA 1998. American Society for Histocompatibility and Immunogenetics, Lenexa, 1998;79.

HLA Dictionary

1. Holdsworth R, Hurley CK, Marsh SGE, Lau M, Noreen HJ, Kempenich JH, Setterholm M, & Maiers M. The HLA Dictionary 2008: 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. Tissue Antigens 2009; 73:95-170.
2. Schreuder GMTh, Hurley CK, Marsh SGE, Lau M, Fernandez-Vina M, Noreen HJ, Setterholm M, Maiers M. The HLA Dictionary 2004: a summary of HLA-A, -B, -C, DRB1/3/4/5, -DQB1 alleles and their association with serologically defined HLA-A, -B, -C, -DR and -DQ antigens. Tissue Antigens 2005; 65:1-55.
   Schreuder GMTh, Hurley CK, Marsh SGE, Lau M, Maiers M, Kollman C, Noreen HJ.
   The HLA Dictionary 2001 : a summary of HLA-A, -B, -C, DRB1/3/4/5, -DQB1 alleles and their association with serologically defined HLA-A, -B, -C, -DR and -DQ antigens. Tissue Antigens 2001; 58:109-140.
3. Schreuder GMTh, Hurley CK, Marsh SGE, Lau M, Maiers M, Kollman C, Noreen H.
   The HLA Dictionary 1999 : a summary of HLA-A, -B, -C, DRB1/3/4/5, -DQB1 alleles and their association with serologically defined HLA-A, -B, -C, -DR and -DQ antigens. Tissue Antigens 1999; 54:409-437.
4. Hurley CK, Schreuder GMT, Marsh SGE, Lau M, Middleton D, Noreen H.
   The search for HLA-matched donors : a summary of HLA-A* ,-B*, DRB1/3/4/5* alleles and their association with serologically defined HLA-A, -B ,-DR antigens. Tissue Antigens 1997; 50:401-418.

Worldwide Participation

Program Information

Collaborative efforts through international and regional workshops have played major roles in advancing HLA typing. Since 1974, the International Cell Exchange has played an important role in improving HLA typing in the interim between workshops.  The main goals are:

• Document the progress of tissue typing
• Standardize typing of established specificities to attain international agreement
• Identify new variants
• Identify serologic equivalents for alleles with little or no serologic information
• Aid developing laboratories to identify "trouble areas," such as serum screening panels and procedures

Proficiency Testing Programs offered:

Many laboratories use our programs to fulfill their external quality control needs. In 2006, over 200 laboratories throughout the world actively participated in our exchange programs. Nearly half of the participants were laboratories outside the United States, affirming that our Exchange is truly an international collaboration.

Report Nomenclature

The acceptable allele and antigen names are the designations recognized by the WHO Nomenclature Committee.  For lists of current HLA class I and class II allelges, please go to http://hla.alleles.org and click on "Alleles" at top of page.

For more information regarding HLA nomenclature changes, visit their website. The nomenclature changes will be officially introduced in April 2010. Lists of old and new allele names will be made available through the IMGT/HLA Database at http://www.ebi.ac.uk/imgt/hla and will be published in Tissue Antigens.