The V region sequence of lambda Bence-Jones protein Wh: evidence for separate germ-line sets within lambda-subgroups

Area of Science:

• Immunology
• Molecular Biology
• Protein Chemistry

Background:

• Bence-Jones proteins are monoclonal immunoglobulins.
• Glycosylation is a common post-translational modification in proteins.
• Complementarity-Determining Regions (CDRs) are crucial for antibody-antigen interactions.

Purpose of the Study:

• To analyze the complete variable region sequence of glycosylated Bence-Jones protein Wh.
• To compare the CDR sequences of protein Wh with other glycosylated Bence-Jones proteins, specifically Nei.
• To investigate potential relationships between Bence-Jones proteins based on CDR sequence similarities.

Main Methods:

• Complete variable region sequencing of Bence-Jones protein Wh.
• Comparative analysis of CDR sequences between proteins Wh and Nei.
• Cluster analysis of available V lambda sequences.

Main Results:

• Proteins Wh and Nei, both glycosylated Bence-Jones proteins of the lambda-subgroup, exhibit identical hypervariable segments in their first and third CDRs.
• Carbohydrate attachment occurs at identical sequences within the third CDR for both proteins.
• The first CDR sequences differ by only one amino acid out of fourteen, indicating high similarity.
• Cluster analyses support a potential
• set
• relationship between proteins Wh and Nei, analogous to mouse V kappa isotypes.

Conclusions:

• The high degree of sequence identity in CDRs suggests a close evolutionary or germ-line origin for Bence-Jones proteins Wh and Nei.
• These findings support the hypothesis of a
• set
• relationship within the lambda-subgroup of Bence-Jones proteins.
• CDR sequence comparison is a sensitive method for reflecting germ-line V gene similarities and inferring protein relationships.